Despite the introduction of newer, less toxic antimicrobial agents, the aminoglycosides continue to serve a useful role in the treatment of serious enterococcal, mycobacterial, and gram-negative bacillary infections. Gentamicin, because of its low cost, remains the aminoglycoside of choice in hospitals with low levels of resistance among Enterobacteriaceae and Pseudomonas aeruginosa. Typically, it is administered in combination with beta-lactam antibiotics, but it may also be used as monotherapy for urinary tract infections or tularemia. Amikacin is useful against gentamicin-resistant gram-negative bacilli and also in the treatment of infections caused by susceptible Nocardia and nontuberculous mycobacteria. Streptomycin serves an important role in the treatment of multidrug-resistant tuberculosis and may be useful in the treatment of some gentamicin-resistant enterococcal infections. Despite an alarming increase in aminoglycoside-resistant enterococci, most institutions have noted little change in patterns of resistance among gram-negative bacilli. Although the development of newer, less toxic aminoglycosides is unlikely in the near future, single daily dosing regimens have been proposed as a convenient, cost-effective strategy. In selected patients, this novel approach seems to be as safe and effective as traditional, multidose regimens.