A Train-Wreck Waiting To Happen: Managed Code and the Windows Shell
The CLR has a major design flaw; each process can only have one. Say for example you have two add-ins for Outlook, where one requires CLR 1.1 and the other CLR 2.0. If the CLR 2.0 is loaded first, the 1.1 add-in will be forced to use the 2.0 runtime. If the one that needs CLR 1.1 is loaded first, the other one cannot be started at all.
Things get far worse when your add-in is an in process extension for the Windows shell. Suddenly the CLR version used by the extension is forced upon every application that displays a file open dialog. Essentially this means managed shell extensions are time bombs set to go off the next time the CLR is updated. Jesse Kaplan and Raymond Chen discuss this more detail.