Once while playing water volleyball I smashed my right hand up against the edge of the pool and got a minor sprain. It hurt so much to use the mouse that I moved the mouse to the other side of the keyboard and flipped the button mappings.
After my right hand got better I realized I liked being able to keep a notepad to the right of the keyboard. It made it easier to jot things down without having to turn away from the computer, so I've used my mouse lefty ever since.
It's funny how many people will see the mouse and "gee, I didn't realize you were left handed" and then get a really puzzled face when I reply "but I'm not".
While I use a mouse at work, I use a trackball at home. Also lefty due to the pool incident.