Lincomycin, produced by Streptomyces lincolnensis, is a lincosamide antibiotic, which inhibits the protein biosynthesis of bacteria, and widely used to treat the infectious diseases caused by the Gram positive bacteria in clinic. Lincomycin biosynthetic gene cluster (lmb) was cloned and sequenced. Biosynthesis and regulation of lincosamide and propylproline were extensively elusive with the breakthrough of S-functionalization of lincomycin. This article reviewed the recent proceedings and achievements on the process of lincomycin biosynthesis.