Nontuberculous mycobacteria (NTM) are generally hardy, ubiquitous environmental bacteria that vary in geographic distribution and pulmonary pathogenicity. Relatively few of the more than 115 species of NTM have been associated with lung disease. Diagnosis of disease due to NTM relies on a combination of clinical, imaging, and microbiologic data. Because NTM may present as acid-fast bacilli in respiratory secretions of patients with clinical and radiologic features that mimic tuberculosis, laboratory discrimination of NTM from Mycobacterium tuberculosis is a priority. This discrimination is now often rapidly achievable using molecular techniques, although some tests have limited sensitivity. NTM species have different antibiotic response patterns, and success with medical treatment alone varies. Macrolides are an essential component of therapy for many species but must be combined with other drugs.