The only difficulty is Expert Realism.

I mostly played L4D all on my lonesome because I'm a little Jonny no-mates. So I have a hell of a time if I play on Expert. How to do it depends on the level and its quirks - I do the first level of Dark Carnival really slowly and methodically because it's mostly safe to, attacks are pretty rare. Conversely, you have to charge like a maniac through The Mall because attacks start before you even leave the safe room and they just. Don't. Stop.

Also god help you if the AI decides it'd be funny to arse around. The number of times I died on the Coaster because those halfwits can't navigate the tracks... oy vey...