Aminoglycosides are efficacious agents. Their use has declined partly because of the development of newer, presumably less toxic agents. Research shows that aminoglycosides can be dosed differently than in the past, maintaining efficacy while reducing aminoglycoside toxicities. Aminoglycosides administered with newer agents may help overcome antibiotic bacterial resistance and thus yield safe and more effective therapy. This study focused on the efficacy and safety of the aminoglycosides extended-interval dosing regimen and was conducted by a search of the literature. Data from The Mount Sinai Hospital regarding bacterial resistance patterns were collected. A nomogram describing the administration of the extended-interval dosing regimen is provided. Extended-interval dosing of aminoglycosides is as efficacious as administering these agents every 8 hours and may result in lower rates of toxicities. Extended-interval dosing also may cost less and be easier to administer. Aminoglycosides are less susceptible to bacterial resistance than many of the newer, currently favored antibiotics. Increasing the usage of aminoglycosides is likely to be safe and beneficial in the treatment of certain bacterial infections.