Lefties are tough to play against simply because you have less opportunities to play against them in practice (so you tend to run into them in tournaments). In addition, the mental block really starts out when you're little and they tend to have the geometric advantage on you because their cross-court forehand goes into your backhand (which may, initially, be the player's weakest shot). Of course, your forehand can go to their backhand but not if you spend a lot of time playing to beat righties (i.e., focusing on inside-outs). So here are some tips for playing against lefties that you might find useful.
A. When returning on the deuce side, stand just a tad closer to the middle of the court to take away their slice serve down the T. Remember that a well struck lefty slice will curve away from you so you have to be just a little closer to the ball. Also, it may sound a bit counter-intuitive but I would recommend returning (with the backhand) towards the ad side of the court. Normally, this opens up the lefty-forehand, but remember that you are moving towards the middle yourself so they don't have that much of an advantage. Aiming cross-court (inside-out backhand) from the deuce side is somewhat risky because your face of the racket is angled outwards and there is chance that the ball will ricochet wide off your string bed. If in doubt, pound the middle of the court.
B. When returning on the Ad-side, position your left foot (and, consequently, your left shoulder) further out in front than normal. That is, you should be at a slight angle in order to intercept the slider. If you wait with your feet/shoulders parallel to the baseline, the slice serve will move away from you. You want the ball to come into the strike zone. Unlike returning from the deuce side, in this instance I recommend sticking the return cross-court. This way, you don't have to change the angle of the ball (i.e., you're basically returning the ball towards the location from where the serve is struck) and your opponent will be forced to either hit a forehand down-the-line (relatively risky) or right back to you. As mentioned before, I am really not in favor of giving the opponent cheap points. And although going down the line (towards the lefty backhand) with the return seems to be the obvious choice, this is somewhat of a risky play due to the geometry and physics (i.e., angle of refraction; vectors) but also because you're probably not all that used to returning down the line against righties (where they burn you with the cross-court forehand). As stated above, again, pound the middle when in doubt and neutralize the lefty advantage.
C. When it comes to being in an actual rally with a lefty, try to utilize the cross-court slice with the backhand in order to neutralize the lefty forehand. Most of the time, they will prefer to hit it right back cross-court rather than opening up down the line (where they set up your forehand). So, if you're ready for the return to the backhand, you can set up the down-the-line backhand (or inside-in forehand) and hit an aggressive shot to their backhand. In this regard, I recommend stepping inside of the baseline as a follow up in order to cut off the reply with another forceful shot.