Mvvm light icleanup and messenger unregister in VB.NET?

When viewmodels should be "cleaned up" depends on your application and viewmodels usage. For example, I work on application with tabbed interface. When user closes tab application calls cleanup on viewmodel representing that tab (which itself goes through its viewmodels and calls cleanup on them as well).

So the general rule - as soon as you don't need viewmodel anymore - you should cleanup it (closing child window, tab, etc.) As for the other questions.

I've not used the Messenger in MVVM-Light so I do not know if there is an inherent way to cleanup. Here are some general answers to these questions.

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