The nontuberculous mycobacteria (NTM), especially Mycobacterium avium complex, are being recognized with increasing frequency as clinical pathogens, not only as a cause of disseminated disease in patients with AIDS but also as a cause of chronic lung disease in patients without AIDS. These infections have traditionally been difficult and frustrating to treat; however, the introduction of new agents, such as clarithromycin, azithromycin, and rifabutin, has significantly improved outcome for patients with some NTM infections. The new therapeutic regimens can be associated with severe toxicities and drug interactions that dictate the need for careful monitoring of patients undergoing treatment for M. avium complex disease. Clinicians will be called on with increasing frequency to determine the significance of NTM isolated from their patients. This determination will require knowledge about the pathogenicity and the appropriate therapy of a variety of NTM species.