Although newer antimicrobials look promising for the treatment of serious Gram-negative infections, the aminoglycosides still remain part of the mainstay of their therapy. Traditional intermittent therapy is based upon the premise that high serum aminoglycoside concentrations are toxic. However, the rate of bacterial killing for aminoglycosides is also a concentration-dependent phenomenon. An animal model of pseudomonas pneumonia and staphylococcal endocarditis has been used to examine the efficacy of non-traditional aminoglycoside dosing regimens, i.e. single, large daily doses or constant infusions, versus the conventional, intermittent low doses of aminoglycosides. Results demonstrate that high peak concentrations are more efficacious. Other recent data suggest that toxicity might also be less with the large, single daily-dose regimen. The way in which we have been dosing aminoglycosides may not be maximizing their therapeutic potential, nor minimizing their toxicities.