Mycobacteria elaborate a great variety of glycolipids of rather exotic structure. Some of these lipids are abundant cell envelope components and are exposed on the bacterial surface. These comprise the species-specific phenolic glycolipids, glycopeptidolipids, sulfatides, and lipooligosaccharides, and the ubiquitous phosphatidylinositolmannosides. Because pathogenic mycobacterial species are facultative intracellular parasites that infect and reside in host cells, some of them may represent potential virulent factors as they have been shown to inhibit both macrophage antimicrobial activities and lymphoproliferation. These biologic activities may derive, at least in part, from the modulation of the cell functions through the interactions between host membranes and these surface-exposed lipids whose structures are different from those of mammalian cell membrane components. In few cases purified glycolipids have been shown to profoundly affect the physical and functional properties of biologic membranes. Therefore, the enzymes involved in the biosynthesis of the biologically active glycolipids represent potential drug targets. However, definite proofs of their implication in the mycobacterial pathogenicity are lacking. Mutants unable to elaborate defined glycolipids are needed.