If you are on mac a wireless magic trackpad
can be an incredible revelation.
I have been through years of mice, then a wacom, then back to mice, and now with the trackpad I don't think I could use anything else. It has taken me quite a while to really get fast and accurate with it - and I still stumble a fair bit - but my general level of comfort and feeling of fluidity with the computer is infinitely better than any alternative.
The other thing that is important is good posture. Basically if everything is less than 90 degrees but more than 60-70 degrees you should be comfortable.
Any angle past 90 degrees can cause a lot of pain. When I say everything I mean, ankles, knees, waist, elbows, wrists, fingers. Basically wherever there is a joint/bend in your body.