However, if the user can and they expect to do it, but is in a mode/state which doesn't allow them to do it, greyed out buttons absolutely.
In some cases, greyed out buttons should be clickable (eg. forms) and that should tell the user what is wrong. Looking at you, billion dollar airline, where I couldn't complete my checkin due to this annoyance.
Also, what happened to hover messages and little (?) marks? Every software behaves like it expects me to know what to do from Day 1.