The worldwide epidemic of AIDS has introduced the need for compounds with activity against mycobacteria. Furthermore, resistant strains both of Mycobacterium tuberculosis and of Mycobacterium avium have been isolated from patients with increasing frequency. This review focuses on new antimicrobials with in-vitro or in-vivo activity, or both, against mycobacteria, such as new rifamycins, quinolones, nitroimidazoles, oxazolidinones, macrolides, and tetracyclines.