It is clear that we have still not exhausted all the restriction endonuclease specificities to be found in nature. Recently discovered BsmI is the first endonuclease recognizing a nonpalindromic sequence that cleaves within the site. Certainly other endonucleases belonging to this class will soon be discovered. More endonucleases are now being sought that recognize longer recognition sequences, because large fragments can now be readily separated by pulse-field electrophoresis. New sources of endonucleases are also being found; for example, a group of viruses that grow on Chlorella algae produce type II-like site-specific endonucleases. As the number and variety of known restriction endonucleases increase, the number and variety of applications keep pace. There is still no end in sight.