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The past year has seen a number of dramatic developments relating to the therapy of mycobacterial disease. The first definition of specific genetic alterations responsible for drug resistance in Mycobacterium tuberculosis occurred and included the deletion of the catalase gene (isoniazid) and mutations in the β-subunit of the RNA polymerase gene (rpo B) (rifampin). Clustered outbreaks of multidrug-resistant tuberculosis in AIDS patients were reported, primarily from New York and Florida. The first successful drug trial for prevention of disseminated Mycobacterium avium complex was reported with rifabutin. The first large series of patients with disseminated M. avium complex treated with clarithromycin was published, as well as a number of other studies looking for the best other agents to include with the new macrolide. The excellent activity of clarithromycin both in vitro and in a clinical trail, were shown for the rapidly growing species Mycobacterium chelonae. This review focuses on the results of these and other recent studies and their impact on mycobacterial drug therapy.