Why does the debugger suddenly stop working

I’m using Unity 4 with the built in MonoDevelop.
I can usually debug my project fine (place breakpoints, step through code, etc.) but every once in a while the breakpoints will stop working.

I go through all the steps (attach to process, and all that), but any breakpoint I place won’t get activated despite the project running fine.

It seems the only sure way to fix this for me is a full system restart.

Is there any reason why suddenly Mono Develop would fail to attach to Unity or why breakpoints won’t get hit (assuming no problem with the code.) Why does debugging with Mono Develop sometimes suddenly stop working?

I don’t use the debugger but sometimes I get a similar situation where Mono and Unity seem out of synch. Instead of a full restart, if I do Assets / Sync MonoDev Project, that goes away.

Yeah, that happens to me too. Sync helps, but it doesn’t solve my debug problem. Seems that sometimes it’ll fix itself, sometimes it wont.
I’d love to at least know what causes it, even if there is no fix.