Aminoglycosides are still widely used alone or in combination with a beta-lactam antibiotic for the treatment of severe Gram negative infection. Oto- and nephrotoxicity are the major side effects associated with the use of these drugs. Although several risk factors associated with aminoglycoside nephrotoxicity have been identified, only few therapeutic approaches were suggested to reduce the incidence of their toxicity in patients. The single daily injection is the only approach actually used to reduce the renal toxicity of aminoglycosides in patients. However, the relationship between the nephrotoxicity of aminoglycosides and the time of the day these drugs should be given has never been explored in patients. Data obtained in laboratory animals indicated that temporal variations can be detected in the renal toxicity of aminoglycosides: the nephrotoxicity was observed during the rest period of the animals while no toxicity was found at other times of the day. Other studies suggested also that food intake can modulate the temporal variations in the nephrotoxicity of aminoglycosides. A better knowledge of the risk factors associated with the renal toxicity of aminoglycosides, a reduction in the number of daily injections of aminoglycosides, administration of aminoglycosides at the time of the lowest toxicity of the drug in patients submitted to an appropriate diet are the most interesting approaches to reduce the incidence of the renal toxicity of these agents.