Before you drill a hole in acrylic be sure that you have an acrylic bit. If a standard drill bit is used, the acrylic won't actually be cut. Instead, the drill will be pulled into the acrylic, and the plastic will travel up the bit. Most likely you'll also crack the acrylic.

Here's what an acrylic bit looks like. They are a bit pricey, but they do the trick.

If you're using a hole saw, you probably won't need to worry about cracking the acrylic if edge of the hole saw is more than an inch away from the center. It's still adviseable to drill the center hole with an acrylic bit.

Some good diagrams and reference links