Apple - Restarting speakers without rebooting?
Try restarting the daemon process that processes audio by typing in Terminal:
sudo killall coreaudiod
This should reinitialize the audio and perhaps reload drivers.
Sometimes changing the sound output from your system preferences > sound panel will reinitialize the connection to your hardware. If you only have one output device available, try installing soundflower, just to have a second output in your list that you can cycle through.
Also: setting things back up after a reboot is a snap with snow leopard. It can remember which apps you had open and reopen them for you.
Try quitting CoreAudio from activity monitor, forcing it to relaunch itself.