- like they said there is a limited ("most" new hardware has x64 drivers or they are in development, so if your only card you put in your machine is video you are fine) driver support.
- Some older software does not work (and a limited number of new software such as splinter cell 3 (last i heard))
- Few CD-mounting apps (but daemon v4 should be out this month), and the ones that are out have some problems (like only mounting ISO's)
+ Large programs (photoshop, dreamweaver, windows) load faster
+ Less lag (in performance not network speed) in games, you usually don't see more FPS, but you usually don't get as laggy (such as in RTS's when you have a ton of units on screen)
+ Control Panel Loads extremly quickly

(this always buged me in win32)
+ More stable (as said based of win2k3 SP1 and NT 5.2)
+ "some" better spyware protection (some of the spyware won't install itself, as it doesn't seem to be compatible)
+ The feeling of knowing your running "state of the art" software while all your friends are still stuck in the age of 32-bit

And you can always check here to see if there is drivers:
http://developer.amd.com/drivers.aspxsry for some of the repeat answers that were already given, just wanted to "show my support".
IMO unles you can't find drivers for your hardware, or you can't run some of your software on it there is on legitamate reason not to use it .