To clarify a bit of confusion here:
"Windows on Windows 64" is the bridge between 32-bit processes running on
Windows x64 and the native 64-bit OS. If you are running a 32-bit program on
Windows x64, you are using WOW64. The only time you are not using WOW64 is
if you are running a 64-bit native application.
Note that the next version of Windows Server, Windows Server 2008 R2, will
allow adminsitrators to disable WOW64 completely meaning that only 64-bit
native applications can run on that system.
Generally speaking, 32-bit applications on Windows x64 just work becuase of
WOW64. The problems come up when there are bugs in the install process (like
they hard-code the installation path or reject valid characters like "(" or
")" in path names), when the 32-bit program contains old-school Windows
3.1-era 16-bit code (usually older installers because this stuff was left in
for years after it was no longer needed), or if the program requires the
presense of a custom kernel-mode driver because all kernel-mode drivers for
Windows x64 must be provided as 64-bit native Authenicode signed drivers.
This last issue affects copy-protection schemes used in some games.
See 64-bit Programming for Game Developers
SDE, XNA Developer Connection
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