With VMware vSphere Storage vMotion, moving running virtual machines from one drive to another is a snap. Once a smaller drive has been emptied of all data, there's a chance you wish to remove it, but only when you're absolutely positive you're removing the correct drive. Perhaps the drive is going to be wiped or disposed of, so don't care about the data on it at all. But you do care about all your other drives and the virtual machines using those drives, so tread lightly.
You can safely remove a drive without shutdown of your ESXi server, if you have configured your motherboard's BIOS to set the on board SATA ports as hot unpluggable, and you're able to reach the drive bay safely while the server is running.
Once the drive is disconnected, be sure to allow it to spin down, then remove it carefully, without bumping other drives or case components. This procedure should be "rehearsed" before you have precious data loaded onto your ESXi system, as there are a wide variety of motherboard chipsets that may, or may not, work reliably for hot-swapping.
In this video, you'll see tips on using vSphere Client to identify the serial # of the drive. This should match the physical drive's sticker, so you know what you're about to remove. I'll also cover how to check if the drive you're about to eject is formatted as VMFS or NTFS. I don't cover ways to dismount in via CLI or SSH or anthing fancy, I'm really assuming the removed drive is about to be repurposed or reformatted or disposed of.. Finally, I also cover how to remove the "phantom" greyed-out drives from the storage pool inventory.
Of course, you can also insert drives while ESXi is running as well, just be sure to Rescan, then check for any filesystems that might be on that drive, before you go ahead and format it as VMFS!
Please let us know if you'd like to see more short posts and videos like this one, with a quick comment below. Enjoy the show!
Jan 24 2012 Update:
you may also want to review this article, [Unpresenting a LUN in ESXi 5.x](http://kb.vmware.com/selfservice/microsites/search.do?language=en_US&cmd=displayKC&externalId=2004605 )
Jan 30 2012 Update:
see also this newer article and video here: