Mycobacterium leprae infection (i.e., leprosy) is a disease that has been recognized—and often misunderstood—since ancient times. The emergence of HIV/AIDS and the development of newer culture methodologies and molecular diagnostic tools have brought about increased interest in the epidemiology, diagnosis, and treatment of human infections from nontuberculous mycobacteria (NTM). More than 140 species of NTM have been identified; approximately 50 of these may be pathogenic for humans, causing a broad spectrum of disease. This chapter covers both M. leprae and selected NTM organisms, including M. avium complex; M. kansasii; M. marinum; and rapidly growing mycobacteria such as M. chelonae, M. fortuitum, and M. abscessus. The section on leprosy encompasses subsections on diagnosis, clinical manifestations and classification, laboratory studies, treatment, and leprosy reactions. Treatments for nontuberculous mycobacteria infections are also covered. Figures include a natural history of leprosy, tuberculoid leprosy, lepromatous leprosy, and various forms of borderline leprosy, as well as type 1 and type 2 leprosy reaction. Tables include the Ridley-Jopling classification of leprosy, recommendations for treatment of leprosy, clinical characteristics and treatment of leprosy, major clinical syndromes associated with nontuberculous mycobacterial infections, diagnosing nontuberculous mycobacterial lung disease, a listing of slow and rapidly growing mycobacteria that are human pathogens, plus treatment regimens for selected nontuberculous mycobacterial infections in adults. This review contains 59 references.