I've had this issue with Sony PRS505 and iRex DR1000s - more often than not, if I attach the device to the computer using a USB connection, calibre will not recognise the device. I can't say if there are certain circumstances where it works (or not), just that it so often don't work that I by habit stop and restart calibre if I have to connect a device while it's running. Interestingly enough, Kindle has worked perfectly for me in this regard. I'm running OS X 10.6 BTW. I haven't used calibre enough on a Windows system to say if there is any difference for me.
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