Thiopeptide antibiotics, such as thiostrepton, are a group of highly modified peptide metabolites. The core scaffold of thiostrepton is a macrocycle containing a dehydropiperidine ring.  This macrocycle is decorated with several dehydrated amino acids and thiazole rings in addition to a second quinaldic acid-containing loop. We recently identified the biosynthetic gene cluster for thiostrepton in Streptomyces laurentii and established that thiostrepton is derived from a ribosomally synthesized peptide. The thiopeptides are, in fact, a newly recognized family of bacteriocins and are subjected to extensive posttranslational modification during prepeptide maturation.  Our progress in delineating the biochemical steps toward thiostrepton biosynthesis will be discussed.