The incidence and prevalence of lung disease caused by nontuberculous mycobacteria (NTM) are increasing worldwide. Environmental sources of NTM include water, soil, and dust, and the acquisition of NTM infection depends on sufficient environmental exposure, host susceptibility factors such as immunocompromised status or cystic fibrosis, and mycobacterial virulence factors. The development of molecular methods has allowed the characterization of new species and the identification of NTM to the precise species and subspecies levels. Mycobacterium avium complex, M. abscessus complex, and M. kansasii are the most frequently identified organisms causing lung disease. Susceptibility to disease is incompletely understood, and thus, it is unclear what preventative measures may be effective. Additionally, NTM have natural and acquired resistance mechanisms to several antibiotics. Better understanding of the ecology, pathogenesis, and mycobacterial genetics and antibiotic resistance mechanisms is essential for preventing NTM infections and developing new regimens for effective treatment.