Publisher Summary The chapter gives an account of the modification of lincomycin. The fermentation broth of streptomyces lincolnensis var. lincolnensis, a new species of streptomycete isolated from a soil sample collected in Gering, Nebraska, was found to contain a new antibiotic, named lincomycin. The announcement by Mason and coworkers of the discovery of lincomycin coincided with chemical and physical characterization of the crystalline hydrochloride. Initial reports indicated that lincomycin possessed good in vitro and in vivo potency against a variety of gram-positive microorganisms. The chapter lists lincomycin-related antibiotics, such as Celesticetin and Lincomycins. It describes the clinical modification of lincomycins and microbial modification of lincomycins and clindamycin, giving details of sulfoxide formation and phosphorylation. Chemical and microbial modifications of lincomycin have succeeded in producing derived antibiotics possessing greater potency, extended spectrum including antiparasitic activity, improved taste, and varied absorption characteristics.