When iTunes is NOT running, does the shuffle show up on the Desktop, or appear in Disk Utility (when you run it)? Or, if you run System Profiler
Apple Menu -> About This Mac -> More Info -> System Report (if running Lion)
does the shuffle appear as a device under Hardware/USB?
If it is being recognized by the Mac in some way, you may be able to get it working again, using the iPod Reset Utility
This utility is for 1st and 2nd gen iPod shuffles only, as a "lower level" reset when you can't do a regular Restore in iTunes.
If the Mac is not seeing the shuffle at all, there is probably a problem with the USB connection, probably the USB cable/dock or the connection point on the shuffle (headphone jack) becoming faulty. To rule out the USB port in the Mac, be sure to try different ports. If you have been using a USB hub (or the spare keyboard port), be sure to try a direct port on the Mac. And be sure to try it with ALL other USB devices (except standard mouse and keyboard) disconnected, in case there is some USB device conflict happening.