Despite their nephrotoxic and ototoxic side effects, AG remain useful antibiotics because of their major, rapid, and dose-dependent bactericidal effects. Combination therapy with an AG appears particularly important in neutropenic and other high-risk patients to provide broad-spectrum bactericidal activity, synergism, and reduction of emergence of resistant pathogens. OD AG therapy is associated with high peak levels in serum that maintain efficacy and low-to-undetectable trough levels in serum that attenuate the risk of toxicity. Administration of short-term OD AG therapy to patients not at risk without renal impairment may not absolutely require dosing monitoring. This therapeutic strategy has been proved useful in clinical trials, now including febrile episodes in neutropenic patients, but it should be avoided during infections in which antimicrobial synergism is required, such as enterococcal endocarditis.