The problem with playing lefties is two-fold: first, their shots come out differently than righties, and second, your natural ball placement to a righty is usually wrong against a lefty. The first part is more or less a matter of playing lefties until you get used to how their shots come out. The two shots from a lefty that most commonly mess up a righty are aggressive crosscourt backhands to the wide forehand, and their serves, especially forehand serves into your forehand that break away. (Hint - if you wait until the last second and then lunge for the ball as it breaks away, you're probably going to miss. Since you probably lower your racket as you lunge, you will probably go long.) It's just a matter of getting used to these shots.
One trick for returning a lefty's forehand serve into your forehand is to aim the ball down the line to the lefty's forehand. The lefty has to be ready to cover that shot, and so at the last minute you can take the ball crosscourt into their backhand. (This is assuming they are stronger on the forehand; if the reverse, you may do the reverse.)
Assuming you are comfortable against a lefty's shots, then the key becomes tactical. Where do you want to play your shots? For example, against a righty, you might play steady shots to the backhand, knowing the opponent can't put his backhand through you - but now that same shot goes into a lefty's forehand, where he may have more power. Or you might play quick shots to a righty's forehand, if your backhand is quicker than the opponent's forehand - but now that shot goes into a lefty's backhand, which not only may be as quick or quicker than your backhand, but also gives him that wide angle into your forehand.
So you may want to rethink your basic ball placement shots - but also use the reverse. Against a lefty, now you can hit quick, aggressive backhands crosscourt into their wide forehand; now you can lock them up on their backhands with your forehand into their backhand. Plus now you can use your own forehand pendulum serve that breaks into their forehand. (Though here the lefty has an advantage - he's probably more used to a righty doing that to him than you are used to a lefty doing it to you.)
So there are really three basic keys to playing a lefty - the aforementioned getting used to their shots and ball placement. However, the latter is really two things - learning (instinctively) what shots you do against righties that you don't want to do against lefties, and learning (also instinctively) what shots you normally don't do against righties that work against lefties.