OBJECTIVE To review the epidemiology, clinical manifestations, diagnosis, and treatment of nontuberculous mycobacterial infections other than Mycobacterium avium complex (MAC). METHODS A MEDLINE search of English-language literature pertaining to nontuberculous mycobacteria other than MAC was performed. Additional literature was obtained from reference lists of pertinent articles identified through the search. METHODS All articles were considered for possible inclusion in the review. Information judged by the author to be pertinent was selected for discussion. RESULTS Mycobacterial infections, including those caused by nontuberculous mycobacteria other than MAC, have assumed greater importance over the past decade, due in part to the changing spectrum of immunosuppression as manifested by organ transplantation and HIV infection. Many pathogenic nontuberculous mycobacteria have been identified that are associated with a wide variety of localized, organ-specific, and systemic infections. Of concern, these organisms exhibit variable, species-specific susceptibility to traditional antimycobacterial drugs and other antimicrobials. In addition, long treatment courses and adjunctive surgical therapy are often required to effect cure. Important antimicrobials for the management of these infections include cefoxitin, imipenem/cilastatin, aminoglycosides (other than streptomycin), tetracyclines, macrolides, and trimethoprim/sulfamethoxazole, as well as traditional antimycobacterials. CONCLUSIONS Nontuberculous mycobacteria have assumed an increasing role in disease etiology in both nonimmunocompromised and immunocompromised individuals. Advent of rapid diagnostic techniques and susceptibility testing has allowed the clinician to identify these organisms and initiate effective treatment on a more timely basis with an improved chance for cure. Few therapeutic agents are available for treatment of these infections, many of which are not considered classic antimycobacterials.