The resurgence of tuberculosis and the increased prevalence of atypical mycobacterial infections in immunocompromised subjects have prompted the quest for novel antimycobacterial agents. Fluoroquinolones, such as ofloxacin and ciprofloxacin, might be promising agents for treatment of tuberculosis especially multidrug-resistant tuberculosis (MDR-TB) and infections caused by Mycobacterium fortuitum. Clarithromycin, an important member of the macrolides, has been shown to have activity against some infections due to Mycobacterium avium-intracellulare, M. fortuitum and Mycobacterium chelonae. Rifabutin, being a rifamycin, has been found to be efficacious in treatment of drug-susceptible tuberculosis, although its place in MDR-TB is less certain. Rifabutin in combination with other drugs might constitute active regimens for treatment of disseminated M. avium-intracellulare infections. When used alone, it can be an active prophylactic agent against such infection. Imipenem, a carbapenem, might provide promising treatment for some M. fortuitum and M. chelonae infections. The place of beta-lactam-beta-lactamase inhibitor combinations in the treatment of MDR-TB is uncertain. Clofazimine and aminosidine being riminophenazine and aminoglycoside, respectively, might merit further evaluation as potentially useful agents for treatment of MDR-TB and M. avium-intracellulare infections. However, much broader evaluation of all these agents in clinical settings is still definitely required.