The WOW64 ("Windows on Windows") feature provides the libraries necessary for the apps themselves to run in native mode, plus it plays traffic cop with the needed registry and file location re~direction. On the processor level the binaries also execute natively. No tricks are necessary here because because x64 is an extension/superset of the x86 standard, rather than being something completely new.
A couple caveats:
The first is that (any) 64 bit OS will require native 64 bit drivers. In the time of XP64 this could regularly be an issue, depending on the installation. For Vista 64 it was less of a problem due to Microsoft requiring valid 64 bit drivers for any company wishing to use the Windows Logo. A little rough out of the gate, but largely solved now. For Win 7, Microsoft continue to insist on both sets of drivers, and the driver model has not changed between Vista and 7. Indeed, many of the members here are using Vista 64 drivers in their Win 7 installations.
Secondly - There is a limitation that when running in 64 bit mode that 16 bit code cannot be executed. So if you have stuff like really old games, or old 32 bit games which have 16 bit installers you could have an issue with those. Should there be a want/need, you may virtualize the OS of your choice (XP or Win 2K, or whatever), and run the apps there. The disadvantage to that approach is that hardware acceleration isn't permitted. But the old 16 bit apps were designed for systems which are orders of magnitude weaker than what we have now. So they should run well, regardless.