One family of solutions to the Fermi Paradox is that civilizations die out before they communicate - natural disaster, nuclear war, etc. This sort of calamity seems plausible some of the time but it would need to happen all of the time. What if any sufficiently advanced society inevitably discovers irrefutable proof that free will is an illusion and just gives up?
Depressing. I prefer this.
(This is a joke. For a more serious consideration please read this.)