The Survivor Co-op Game Mode is played out across four sprawling campaigns, set in urban and rural environments. The team of four Survivors may be comprised of one to four human players, allowing for single player and multiplayer co-op games.

The next-generation A.I. technology of all non-player Survivor and zombie characters is a pool of systems used to procedurally generate a unique experience by monitoring the players' experiences and tailoring the pacing and difficulty of action for each game. This makes for a different experience each time the game is played.

In the Left 4 Dead Vs. Mode, play as a Survivor or as one of four types of "Boss Infected." Each of the "Boss Infected" possesses an exceptional mutant ability -- such as a 50-foot tongue lasso or a giant belly full of explosive methane gas -- instead of traditional firearms.