Every now and then after leaving my computer running for several weeks I would get a weird error message when trying to launch Excel saying something like:

C:\PROGRA~1\MICROS~1\Office12\EXCEL.EXE is not a valid Win32 application.

or

This file does not have a program associated with it for performing this action. Create an association in the Set Associations control panel.

I tried several things to make it run again, but only a restarting would solve the problem. Finally, I decided to investigate a bit more and turns out there is a fix that solves the problem that you can download from Microsoft support:

http://support.microsoft.com/kb/952709

This update improves the reliability of Windows Vista SP1-based computers that experience issues in which large applications cannot run after the computer is turned on for extended periods of time. For example, when you try to start Excel 2007 after the computer is turned on for extended periods of time, a user may receive an error message that resembles the following:

EXCEL.EXE is not a valid Win32 application

I just installed it and so far so good, no more weird errors but I guess I need to wait a few weeks before I can testify it works. Either way I though this could be helpful for others.

Direct links for the fix download are:

Windows Vista, 32-bit versions
Download the Update for Windows Vista (KB952709) package now. (http://www.microsoft.com/downloads/details.aspx?FamilyId=DF72A9B0-564E-4326-894E-05CBA709CB39)
Windows Vista, 64-bit versions
Download the Update for Windows Vista for x64-based Systems (KB952709) package now. (http://www.microsoft.com/downloads/details.aspx?FamilyId=C3536CAA-7B71-4525-9D23-21A5B3D4507F)