Do a Control+Alt+Delete, click Process, find Firefox.exe, select it, and hit "End Process." The problem is, sometimes Firefox will close, but won't actually close the program, so when you try to open it, it tells you it's already running, 'cos hey, it is. However, once you manually close it then reopen, it'll be fine.
That's how I do it whenever that happens, however, recent software updates seem to have made that problem occur much less often.
To run your computer in safe mode (which you shouldn't need to do) you turn on your computer, let it start up, etc. all while holding F8 (I believe).