On OS X, it seems like the menus can stop working for some reason. I've noticed it when I had DOM Inspector open, and the menus only didn't work when DOMi was the active window (but I believe switching to a Firefox browser window had the menus working.)
I just encountered this issue after leaving Firefox open (laptop open) overnight. I only had one window open. Disabling the add-on from about:addons and re-enabling let's the menus work again.
... still no idea why or how the menus would become unresponsive in the first place.
Another oddity is that sometimes the menus just start working later even without a restart. I've noticed that disabling doesn't always fix it, and I recall that I've disabled multiple times (in the process of developing) and the menu was still broken. But I don't recall if it was because of the disable/reenable that fixed the menu or if it was just time passing.
It seems like opening about:addons in a tab (without disabling the add-on) can sometimes fix the issue.
This seems to happen in Test Pilot as well for the Search Behavior Study even without the add-on installed. There's been reports of the problem fixing itself without even needing to restart Firefox (and with no add-on to disable/reenable) so just with time passing.