I. Abstract Rapamycin is a bacterially derived natural product with a remarkable history as both a chemical probe for studies of cell growth control-related pathways, and a bona fide drug with established or predicted clinical activities in a variety of disease settings. Rapamycin was first noted as a potent antifungal and immunosuppressive agent, and studies of this drug's mechanism of action revealed that rapamycin was a surgically precise inhibitor of a novel protein serine–threonine kinase, appropriately termed the target of rapamycin (TOR). Intensive research efforts have revealed that the TOR orthologs function in a highly conserved pathway of eukaryotic cell growth control. This review focuses on the impact of rapamycin exposure on the TOR ortholog (termed mTOR) expressed in mammalian cells. We briefly describe the biosynthesis of rapamycin and the chemical modifications of the parent compound that yielded several of the experimentally useful and/or clinically active derivatives, collectively termed rapalogs. We then review in some detail the pharmacology of rapamycin, particularly as it relates to the growth and proliferation of cancer cells. The opportunities and challenges associated with the development of rapalogs as anticancer agents are then discussed. Finally, we briefly review some provocative recent insights into the effects of rapamycin on the immune system and on organismal aging.