Nontuberculous mycobacteria (NTM) are ubiquitous in the environment and cause a wide range of diseases in humans. Pulmonary involvement, the most common disease manifestation of NTM infection, is being increasingly encountered in clinical settings. In addition, specific phenotypic and genetic characteristics of persons predisposed to contract pulmonary NTM disease are now beginning to be recognized. Prior to treatment, patients should meet clinical and microbiologic criteria for NTM disease. Treatment involves prolonged courses of antibiotics in various combination regimens that are often discontinued because of serious side effects. In some cases, complete cure of pulmonary disease is difficult to achieve. Rather, clinical improvement may be a more feasible goal. Surgical treatment is warranted for select patients.