A flash memory device has no moving parts, therefore it does not suffer from increased access times with a fragmented file-system as a mechanical hard drive does.
A common argument in favor of defragmenting a thumb drive is that it makes data recovery easier, since files are contiguous. If you *really* want to “defrag” your flash drive, do so by copying all the files to a temporary location, format the flash drive, and then copy them back. This way, the files are written consecutively, without fragmentation, and only costs your flash device one write per used block. Using a program like Windows defrag would cause thousands upon thousands of writes, reducing the device’s lifespan, and worse, wouldn’t do nearly as good a job as a copy/format/recopy procedure would.
This also applies to so called SSDs, or Solid State Disks. These are also flash memory, and defragmenting them is destructive. Windows XP and on up tend to defragment automatically by default. Windows Vista and 7 do a full defrag on a schedule. THIS IS BAD!! If you are running Windows on an SSD, disable automatic defragmentation via the control panel on these OSes.