The biggest problem with 64bit Windows is that kernel-mode drivers need to be 64bit as well. While newer hardware usually has 64bit drivers, hardware that is slightly older usually does not, and this is where the problems start: your favourite piece of hardware simply won't work. User-mode drivers can be 32bit, by the way.
Mac OS X circumvents this issue by running the kernel in 32bit, allowing 32bit drivers to run without any problems (the kernel in Snow Leopard is supposed to be 64bit). The userland applications run in 64bit, however, so users still get many of all the benefits. The Linux situation is different; here, the advantage of portability and open source come into play: drivers are simply recompiled to support 64bit.
The second problem is 32bit applications. While 64bit Windows is perfectly capable of running 32bit applications, you might still encounter problems, which can be quite annoying. Especially if you rely on certain applications, its 64bit support is something you should take into account.
Mac OS X has all of its important frameworks in 64bit (Cocoa, Quartz, OpenGL, X11), and thanks to the concept of fat binaries, you really needn't worry about what version you download. In the Linux world the transition to 64bit once again benefits from the open nature of the operating system and its tools. While open source may have its downsides, there is no denying that in this case, its strength is pretty obvious.
According to Gizmodo, the time is right to move to 64bit with Windows 7. I personally faced this choice with my new computer, but I decided to stick to 32bit for now when it comes to Windows because I'm not that much of a performance junkie (I don't think Miranda really benefits from 64bit), and I didn't want to be bothered with its potential problems.
So my question to you is: have you ever faced this choice? What were your arguments to go one way or the other? What are your experiences running 64bit Windows or any other 64bit operating system? What major applications or hardware parts failed for you?