Difficulty

There are four difficulty levels in Left 4 Dead. Each level refers to the difficulty of the campaign, and each has drastic differences over the next. For example, on the Easy difficulty, it's rare to see a horde outside of the occasional Crescendo Event, whereas on Expert it's likely you'll face a Horde around every corner. The specific differences between each difficulty level are listed below.

Easy
As the name suggests, this difficulty is the easiest of the four. Players receive a ridiculous over-abundance of health packs, to the point where you can be completely reckless for the whole game and still have plenty of packs left over. Common Infected die from a single pistol shot, meaning that a single player with a pistol can decimate a horde in moments. Shotgun shells kill Infected at sniper range. This mode would be recommended for beginners and experienced players who simply want to relax. This is also a good (albeit somewhat cheap) way of getting some achievements.

Details

 * The Tank has 3000 health points, does 24 damage per hit and 75 when pounding.
 * The Witch has 500 health points and is startled in 8 seconds.
 * Friendly fire does not inflict damage, but friendly fire incidents will still register and disqualify players from earning the Safety First achievement.
 * Molotov cocktails and gas cans, once ignited, can still cause damage to other Survivors, so watch where you throw them.
 * Common Infected inflict 1 point of damage per hit, 0.5 if attacking a Survivor's back.
 * The Smoker does 10 damage per hit on ensnared Survivors and takes 5 seconds to ensnare a Survivor.
 * The Hunter does 6 damage per hit and 5 per hit on pounced Survivors.

Normal
Normal mode is fairly balanced, as far as the difficulties go. It's harder than easy, but not something that will quickly decimate an inexperienced player, such as in advanced or expert. However, the Director's evident sadism will begin to show more often here, especially if the players are doing well.

Normal is also the set difficulty for Versus mode.

Details

 * The Tank has 4000 health points, does 24 damage per hit and 75 when pounding.
 * The Witch has 1000 health points and is startled in 5 seconds.
 * Friendly fire inflicts 10% of the weapon's damage per hit to the Survivors.
 * Common Infected inflict 2 damage per hit in the front, and 1 from the back.
 * The Smoker does 10 damage per hit on ensnared Survivors.
 * The Hunter does 10 damage per hit and 5 per hit on pounced Survivors.

Advanced
Advanced is for substantially more experienced players, however is generally played less than even Expert as it has less to offer in the way of achievements than any other difficulty. Although it's not as devastating as Expert, it demands a high level of competency and care. If the player is not careful, then they should be ready for multiple tries per map, as things can get pretty hard—and friendly fire incidents are the bane of a serious player, as they take off quite a bit of health here. The fact that first aid kits don't spawn very often only serve to further exacerbate the problem.

Details

 * The Tank has 6000 health points, does 33 damage per hit and 75 when pounding.
 * The Witch has 1000 health points and is startled in 5 seconds.
 * Non-headshots get no bonus damage
 * Common Infected inflict 5 damage per hit from the front, and 2.5 from the back.
 * Friendly fire inflicts 50% of the weapon's damage per hit to the Survivors.
 * The Smoker does 20 damage per hit on ensnared Survivors.
 * The Hunter does 20 damage per hit and 10 per hit on pounced Survivors

Expert
Expert mode is, obviously, the toughest difficulty of the four. It is not at all recommended for the inexperienced or impatient, as it may take many tries for the player to complete a single chapter. In this mode, never fear death, and always be on the move. Standing still is an almost guaranteed way to get killed here. But then, even moving has its down sides. The player must be ready for anything, anticipate everything. However, they must remember that in the end, it is very likely that they will die. Though it can get incredibly frustrating at times, with practice and a great deal of patience, it is possible to get through.

There are many unique nuisances in expert difficulty that you won't see in the others.

The Horde
The time between Panic Events in Expert mode is a lot shorter than in the other modes, with around four hordes in three minutes, and the size of the horde is bigger. On top of that, Boomers will constantly be sent at the Survivors, vomiting and exploding all over them. This makes progressing somewhat difficult as they may be stuck within one area for long periods of time attempting to deal with the Infected.

Details
This is a mostly complete list, extracted in part from the exposed cvar interface. See console commands for information on the cvars.
 * The Witch has 1000 health points, can instantly kill a Survivor and is startled in 4 seconds. If Witches are avoided without being startled the Director ensures to continually spawn them in your path, sometimes spawning three or four per level if the player(s) manage to keep avoiding them.
 * The Tank has 8000 health points, deals 100 damage per hit and 150 when pounding.
 * Fire inflicts 40 damage per second to the Survivors.
 * Friendly fire inflicts full damage to the Survivors. Avoid friendly fire at all costs. One shot from a pump shotgun will instantly incapacitate teammate.
 * Common Infected inflict 20 damage per hit from the front, and 10 from the back.
 * First-aid kits are extremely rare on Expert outside of the safe room and before the finale (except for the Death Toll Finale, and in the Ambulance right outside of Mercy Hospital.); They are instead replaced by pain pills, which become surprisingly common.
 * The Smoker does 30 damage per hit on ensnared Survivors.
 * The Hunter does 40 damage per hit and 15 damage per second on pounced Survivors.
 * At close range the Tank is extremely good at cutting off and closing in on Survivors who try and turn, even a little (By turning it any movement other than running directly away from him.) The only way to outrun a Tank on Expert at close range is to continue to run directly away from him. The same goes for his rock-throwing attack, it is absolutely unavoidable if you are not paying attention. The best way to avoid his rock throw attack is to continue to move in one direction while he prepares to throw the rock, then when he throws it change directions quickly. Or simply remain still and move at the right time.
 * The Boomer appears to have increased range with his vomit attack, getting up to the point of almost being able to "snipe" you with it.
 * Enemy reactions are much faster; for example, Smokers will often pause for several seconds on easier difficulties before snaring you with his tongue; however, on Expert, they won't hesitate to attack again.
 * The most threatening Special Infected will almost always spawn on the path(s) you must take, namely the Tank and the Witch. However, observant players might notice a roaring, muscled or hunched, crying mass in the distance, and closed captions can help predict enemy locations, which can help a player get the drop on the Special Infected.

Left 4 Dead 2
Left 4 Dead 2 is to feature a new difficulty level. Not much has been revealed at the current time, other than it's title: Realism. It is more of a "game modifier" as stated by Valve, who went on to say it is for more "hardcore" players. More info will be coming as it is revealed.

It looks as though it can be played on lower difficulties settings such as advanced.