ABSTRACT.Background. There has been a longstanding debate regarding whether aminoglycosides should be administered on a multiple daily dosing (MDD) or once-daily dosing (ODD) schedule. Several unique characteristics of the aminoglycosides make ODD an attractive and possibly superior alternative to MDD. These include concentration-dependent bactericidal activity; postantibiotic effect, which allows continued efficacy even when serum concentrations fall below expected minimum inhibitory concentrations; decreased risk of adaptive resistance; and diminished accumulation in renal tubules and inner ear.Objective. To assess the relative efficacy and toxicity of ODD, compared with MDD, of aminoglycosides among pediatric patients.Study Selection. Randomized, controlled trials among children, evaluating the relative efficacy and toxicity of ODD versus MDD of aminoglycosides, with similar total daily doses in the compared arms, were selected.