It's possible that the drive is going bad - or at least the external enclosure controller is going bad.
Is the drive under warranty still? If not, can you pop the drive out and hook it directly up to your computer to test if it's the drive or the enclosure?
Also, what brand is the drive?
IMO, I would attempt to boot off of a Linux LiveCD, and see if it recognizes the drive plugged in. If it does, then back up any important data off of it that you can, just in case the drive is indeed going bad.
Edit: looks like the Signature Mini line is a company owned by Western Digital. I'd see if their diagnostic tool tells you anything about the drive: http://support.wdc.com/product/downl...upid=612&sid=3