Combinations of beta-lactam and aminoglycoside antibiotics are frequently used in the treatment of pediatric infections. At our institution, amikacin has been the sole aminoglycoside utilized for the past five years. Such regimens are used empirically in specific patient populations to treat the pathogens most likely to be responsible for a symptom complex, e.g., sepsis in the immunocompromised host, pneumonitis in patients with cystic fibrosis, neonatal infections such as sepsis or meningitis, and infections in patients with intestinal perforations. Beta-lactam and aminoglycoside combinations are employed as definitive therapy when synergistic interactions can be predicted, such as in systemic Pseudomonas infections, viridans streptococcal endocarditis, or enterococcal infections. In all of these circumstances, we have utilized amikacin extensively as the sole aminoglycoside, with highly satisfactory results. In vitro antibiotic synergy studies, including those employing aminoglycosides such as amikacin, may be used to predict in vivo antibiotic interactions. However, definitions of in vitro synergy vary with the laboratory method used to evaluate synergy. Furthermore, recent data from our laboratory suggest that the absence of demonstrated in vitro synergy between amikacin and imipenem may not correlate with improved survival of neutropenic rats with gram-negative sepsis that are treated with both agents. Thus, in vitro studies of synergy may underestimate the frequency of improved outcomes with combination antibiotics, especially with amikacin and imipenem. There are potential risks associated with the use of multiple, broad-spectrum antibiotics, including fungal or bacterial superinfection and increased drug toxicity. Although the former is common in pediatric patients, aminoglycoside (amikacin) toxicity has rarely been a problem. Combination antibiotic regimens that include an aminoglycoside such as amikacin continue to have an important role in pediatrics and should be used empirically or definitively for the specific indications discussed.