Mycobacterium tuberculosis (Mtb) lipids are indelibly imprinted in just about every key aspect of tuberculosis (TB) basic and translational research. Although the interest in these compounds originally stemmed from their abundance, structural diversity, and antigenicity, continued research in this field has been driven by their important contribution to TB pathogenesis and their interest from the perspective of drug, vaccine, diagnostic, and biomarker development. This article summarizes what is known of the roles of lipids in the physiology and pathogenicity of Mtb and the exciting developments that have occurred in recent years in identifying new lead compounds targeting their biogenesis.