Nontuberculous mycobacteria (NTM) infections are broadly classified as skin and soft tissue infections, isolated lung disease, and visceral or disseminated disease. The degree of underlying immune abnormalities varies between each classification. Skin and soft tissue infections are usually the result of iatrogenic or accidental inoculation of NTM in otherwise normal hosts. Visceral and disseminated NTM disease invariably occurs in individuals with more severe immunosuppression. Although the focus of this article is to discuss the pathogenesis of NTM lung disease, the risk factors of visceral/disseminated NTM disease are also summarized, as they provide insights into host-defense mechanisms against these organisms.