Depends entirely on the style of illustration you want. What do you have in mind?
Adobe Photoshop (raster) and Illustrator (vector) are good all-around packages. Flash is good for freehand drawing vector.
Then there are digital painting packages that aim to be close to the real thing. Corel Painter and Abmient Design Artrage for instance.
I personally can't go without Photoshop anymore, it has a wide array of image editing possiblities, vector paths and a brush engine you can use to paint with.
I use PS CS4 mostly, but I go without a graphics tablet... I don't have a job, so the money doesn't come that often.
Now I have to use a school laptop, and it only has PS Elements 7. It pisses me off, because it isn't nearly as powerful as CS4, and that's what I'm used to.
Another one I found really good was PS CS3. I know it's older, but in my opinion it's better laid out.