ABSTRACT Nontuberculous mycobacteria (NTM) include species that colonize human epithelia, as well as species that are ubiquitous in soil and aquatic environments. NTM that primarily inhabit soil and aquatic environments include the Mycobacterium avium complex (MAC) ( M. avium and Mycobacterium intracellulare ) and the Mycobacterium abscessus complex (MABSC) ( M. abscessus subsp. abscessus , M. abscessus subsp. massiliense , and M. abscessus subsp. bolletii ) and can be free living, biofilm associated, or amoeba associated. Although NTM are rarely pathogenic in immunocompetent individuals, individuals who are immunocompromised, due to either an inherited or acquired immunodeficiency, are highly susceptible to NTM infection (NTMI). Several characteristics, such as biofilm formation and the ability of select NTM species to form distinct colony morphotypes, all may play a role in pathogenesis that is not observed in the related, well-characterized pathogen Mycobacterium tuberculosis . Different morphotypes of NTM have been recognized and characterized since the 1950s, but the mechanisms that underlie colony phenotype change and subsequent differences in pathogenicity are just beginning to be explored. Advances in genomic analysis have led to progress in identifying genes important to the pathogenesis and persistence of MAC disease as well as in illuminating genetic aspects of different colony morphotypes. Here we review recent literature regarding NTM ecology and transmission, as well as the factors which regulate colony morphotype and pathogenicity.