Development of new antimycobacterial agents has gained impetus from the frequent occurrence of disseminated M. avium complex infections associated with the AIDS epidemic and the resurgence of tuberculosis. Promising new agents are being developed by modification of existing antimycobacterial agents (for example, aminoglycosides, macrolides, beta-lactams, and rifamycins) and by development of new therapeutic classes of drugs (for example, 4-quinolones). In addition, new drug delivery systems (liposome encapsulation) and immunomodulators may prove to be clinically useful in the treatment of some mycobacterial infections. New antimycobacterial agents will likely have their greatest impact on nontuberculous mycobacterial diseases because this is the area in which improved therapy is most needed. The specific role for new agents will be established only after more extensive study in animal models of mycobacterial infection is followed by controlled, randomized clinical trials.