Safe room

The safe room, also known as the safe house, is the way most of the chapters (save for the finales) of Left 4 Dead end. They are barricaded, impenetrable rooms for Survivors to rest inside of in between fending off hordes of the Infected. Safe rooms are easily identified by the big, red, heavily armored, metal doors that they all have. Once all Survivors are inside the room and have closed the door, the next chapter will load. Most safe rooms are equipped with four things: First aid kits, ammunition, weapons (generally Tier 1, but Tier 2 weapons replace them during the last or second to last chapters. Of course it differs from campaign to campaign), and graffiti.

Overview
Safe rooms are the only part of a map where Survivors are completely safe. None of the Common Infected can break down the doors (NOTE: If left alone long enough, Common Infected can break the safe room door down on any difficulty). Of course, if the doors remain open, any Infected may enter the room until the door is closed. If an Infected enters the safe room, it must be killed or pushed out of the room before the next level will load. Common Infected try to reach into the safe room door at the beginning of the level if they notice the Survivors, but usually pose no threat, and can be disposed of very easily. In Versus Mode the safe room door will automatically open after a while, if the survivors do not open it first, and cannot be closed again.

Most of the safe rooms have a decent amount of graffiti in them, left by other unseen Survivors that have come and gone through the safe room. Valve stated in Left 4 Dead's commentary that the safe rooms were intentionally created to fill in some of the plot that Left 4 Dead lacks through setting awareness.

Plot-wise, it seems that CEDA encouraged people to build their own safe rooms. Multiple posters throughout the Left 4 Dead games have instructions showing how to build safe rooms. These instructions are located in actual safe rooms, which raises questions to who built the in-game safe rooms in the first place.

The Survivors

 * If you can, try to be proactive about the Infected outside—shoot what you can see, clear the area for a safer, easier leaving of the safe room.
 * When in Versus mode, try to leave the starting safe house as soon as you can, the quicker the better. The longer you linger will only result in the Infected having a better coordinated first strike against you and your teammates.
 * When in Versus, the safe room door will open automatically after a period of time (about a minute), so it's better to form a plan quickly. When the door is opened, it is recommended that all Survivors leave the room quickly so that the Infected team will not be able to achieve what is referred to by the player community as “Insta-Spawn”, the quick re-spawn of fallen player-controlled Special Infected. This does not occur in campaigns (or in Left 4 Dead 2), so take all the time you need.
 * As everyone knows, the Witch has a nasty tendency to spawn in the way of the Survivors. One easy way to get rid of her without much fighting, assuming you are close to the beginning of a chapter, is to send one healthy (40% health and above; you'll need the speed) Survivor to pester the Witch, and then have them quickly run back to the safe room with her in pursuit. The Witch can't break down the door, and since she is no longer programmed to simply eviscerate everybody, will simply run away at this point, leaving everybody free. This does not work in Versus - The safe room door cannot be closed after being opened.
 * If faced with a Tank on The Subway, but you aren't quite in a position to take it on competently, try to run back to the starting safe room. The Tank will pursue you all the way, but the safe room won't hold him. Try to shoot and run. Use the vent and circle around. Rinse and repeat.
 * On certain levels such as The Crane, Infected can reach through holes in the wall surrounding the safe room and do damage, so stay clear of these.
 * A common trick is to trap the Tank inside the ending safe room and, considering the Tank cannot break the ending safe room door down, will stay stuck inside and can be shot through the door or burned with a Molotov, effectively killing the Tank with little to no bloodshed. This is extremely helpful online, especially on Versus mode, when your health generates points at the end of each chapter.
 * In Left 4 Dead 2, never run into the safe room thinking it is at all safe. The Director may decide to torment you and spawn a Special Infected or two inside the safe room. A rare glitch has even been seen where if both doors are closed but not everyone is inside yet, the director may spawn a Special Infected out of sight on a two-story safe room (such as in the middle of Hard Rain).

The Infected

 * While the door cannot be breached, Infected can sneak in when the Survivors are nearing the goal. Often one person will break away and attempt to run to the safe room, making themselves prime targets for the claws of a Hunter or the tongue of a Smoker.
 * The safe room is the last point where Infected can really team up on the Survivors. Make the most of the final point by organizing in front of the safe room, and then keeping one Infected inside the room for good measure. Try to position a Boomer outside to vomit or explode on your target, as the Horde that will quickly come will further slow the Survivors down.
 * While the Infected cannot spawn until the Survivors exit the safe room, it also gives a good opportunity to organize a powerful first wave. Organize the Infected team early to hit them just as they are coming out. The sooner Survivors are hurt, the sooner Survivors will have to use their first aid kits.
 * Try to hit the Survivors before they enter the safe room as a Tank, even if you spawn very close to the end. Even if the Horde is entering the safe room and have the Survivors occupied, the Survivors may try the trick stated above if they can, which you cannot escape.
 * If your team is skilled enough, try to keep Survivors in the beginning safe room. As long as one Survivor doesn't leave the safe room, you can respawn almost instantly. Also note if all the Survivors leave the safe room and go back in, this no longer works. (This feature is not applied to Left 4 Dead 2.)

No Mercy

 * The Apartments - In the basement of an apartment block next to the subway.
 * The Subway - Inside the store room of the pawn shop, presumably built by the shop's owner.
 * The Sewer - In the staff lounge behind the hospital's main reception desk.
 * The Hospital - In a temporary room in the construction site on the 28th floor of the hospital.

Crash Course

 * The Alleys - In the center of a warehouse.

Death Toll

 * The Turnpike - Inside the generator room of the overflow pipes.
 * The Drains - Inside a converted railway carriage in the train station.
 * The Church - Inside the church's vestibule, guarded by the Church Guy. It is unknown whether the Church Guy built this safe room or simply found it later.
 * The Town - In the back room of a storage garage.

Dead Air

 * The Greenhouse - Inside the kitchen of the Harbor View Hotel.
 * The Crane - Inside one of the storage rooms in the self - storage facility.
 * The Construction Site - Inside a hastily built structure made of wooden boards and metal bars at the entrance to the airport terminal. This is the only safe room in the game that is entirely constructed for this purpose, rather than an existing room that has been converted.
 * The Terminal - Inside one of the airport's passenger jetways.

Blood Harvest

 * The Woods - Inside one of the offices of the train depot.
 * The Tunnel - Inside a maintainance locker room alongside the train tunnel.
 * The Bridge - Inside a wooden shack at the top of the ridge next to the fallen bridge.
 * The Train Station - Inside a converted railway carriage at the end of the railway bridge.

Left 4 Dead 2
In Left 4 Dead 2, each level contains a safe room, with slight differences from the first game's safe rooms. Some safe rooms are larger than the first game's, such as an entire convenience store, as opposed to a single room.

Dead Center

 * The Hotel - At the exit of the hotel lobby.
 * The Streets - The Mall entrance by a parking lot that was being used by CEDA.
 * The Mall - A backroom in The Mall's maintenance corridors.

The Passing

 * The Riverbank - An office room near the park.
 * The Underground - A maintence room on the other side of Rayford near the bridge.

Dark Carnival

 * The Highway - A small shack off to the side of the park's main entrance.
 * The Fairgrounds - The entrance to The Tunnel of Love.
 * The Coaster - The entrance to the roller coaster.
 * The Barns - The entrance to the stadium where The Concert finale takes place.

Swamp Fever

 * Plank Country - A large short pipe under a bridge.
 * The Swamp - A small shack next to The Shantytown.
 * The Shantytown - A small shack near The Plantation.

Hard Rain

 * The Milltown - A small building across the street from The Sugar Mill.
 * The Sugar Mill - A gas station on the other side of the Sugarcane Field. Once the next level loads, the safe room door is switched from an entrance door to an exit door.
 * Mill Escape - Same building as from The Milltown, but with the safe room doors reversed.
 * Return To Town - A small, previously barricaded house with basic medical supplies.

The Parish

 * The Waterfront - A small 99 cent shop.
 * The Park - A maintenance room under an overpass.
 * The Cemetery - The back office of a store.
 * The Quarter - A maintenance room at the base of The Bridge.