The most common disease patterns produced by atypical mycobacteria are pulmonary disease, cervical lymphadenitis, and infection of soft tissue, bones, and joints. The treatment of disease due to atypical mycobacteria can be confusing unless one clearly differentiates the organisms according to clinical characteristics and response to various chemotherapeutic agents. For this reason, we have attempted to simplify the task by proposing a new classification system. The organisms that might be isolated from human material are divided into the following three classes: nonpathogens; those that are easy to treat with standard mycobacterial therapy; and finally, those that are difficult to treat with standard mycobacterial therapy and require other approaches. This new system of classification should help the clinician in dealing with these organisms. Because even the pathogens may sometimes appear as a contaminant in human material, including sputum, one must document that these organisms are associated with disease prior to instituting therapy.