Despite the introduction of several new classes of antimicrobial agents, aminoglycosides are still recognized as first-line therapeutic agents in the management of severe gram-negative sepsis. The major obstacle limiting the use of aminoglycoside antibiotics has been, and continues to be, the possibility of drug-induced ototoxicity and nephrotoxicity. This review critically examines the definitions used to establish the diagnosis of aminoglycoside-induced nephrotoxicity and ototoxicity and the clinical significance of these adverse reactions. The review also focuses on the practical and economic issues surrounding therapeutic drug monitoring practices. We conclude that aminoglycoside antibiotics remain an effective and economical form of therapy for severe infections and that if careful criteria are used in the selection of these agents, the benefits of therapy outweigh the risk of toxicity.