Considerable in vitro and clinical research has been conducted concerning once-daily administration of aminoglycosides. Inherent to such regimens are elevated peak concentrations and prolonged periods during which concentrations are below the MIC for the pathogen. High peak concentration to MIC ratios may maximize bactericidal rates but the problem of toxicity remains. Although sustained exposure to sublethal concentrations could undermine efficacy, antimicrobial activity may be prolonged by the post-antibiotic effect. A wide variety of animal toxicity and efficacy models has been investigated. Findings suggest that less frequent administration is associated with less toxicity while efficacy remains unaltered. Elevated doses appeared to be well tolerated in studies in volunteers and patients, however relatively few critically ill patients have been assessed. Efficacy in the treatment of urinary tract, respiratory and other infections appears unaffected by administration frequency. In an attempt to standardize dosage regimens to allow comparisons among diverse patient groups in clinical trials, guidelines for dosage adjustment based on renal function are outlined.