As much as this is gunna sound like I'm trolling, I recently ran into the same issue and one of the questions I'm about to ask did indeed solve the problem, so don't take this the wrong way. XD
Are the speakers plugged in?
Are they actually receiving power or is the circuit breaker downstairs tripped for some stupid reason?
Are they plugged into the pc?
Is it muted in Windows because some fleepity fleep fleep had music on their page at 4,000% volume?
On Vista/7, is that particular application muted in the mixer because you wanted YOUR music playing?
And, the one I am in fact guilty of, is it actually supposed to be playing music? The DVD "From Paris With Love," for instance, has no menu music, and neither did the DVD I just created for myself. I spent 30 minutes debugging before realizing I forgot to enable menu music. -_-