I have 2 4TB external hard drives and they work fine on XP 64. Didn't have to do anything. They just work.
Edit:
I saw people here talking about 512k and 4k sectors. The thing is this. If you format the drive on Windows 7 or newer the drive will have the 4k alignment as it should by factory. After that, when you plug the drive on XP it will stay that way and it will work without the performance drop you would get if you try to align them to 512 for XP compatibility.