Disseminated Mycobacterium avium complex (MAC) is one of the most common opportunistic infections in AIDS patients and is increasingly recognized as a significant pathogen in chronic pulmonary disease in nonimmunocompromised patients. Important progress in therapy has occurred over the last several years. In AIDS patients, multidrug therapy has been shown to be beneficial in terms of reducing circulating bacteremia and improving clinical symptoms. Clarithromycin and azithromycin, two broad-spectrum antimicrobials with minimal activity against Mycobacterium tuberculosis, have emerged as potent, well tolerated agents pivotal to treatment regimens. In AIDS patients, rifabutin prophylaxis reduced the frequency of MAC bacteremia by 50% in two placebo controlled trials. Despite these advances, there remains a need for determining the optimal combination regimens for therapy, and more effective drugs for prophylaxis which are beneficial both in terms of survival and functional capacity of patients.