The use of antibiotic combinations remains a necessity in certain clinical circumstances but must be approached with care since the drugs combined may prove antagonistic rather than synergistic. A variety of methods involving different principles are used for the evaluation of drug interactions in vitro; each technique has clear advantages and disadvantages. Information from the literature implies that there is generally a reasonable concordance between in vitro and in vivo results with drug combinations but that discordant results are not uncommon. More specifically, in vitro synergy does not always ensure a successful clinical outcome, but lack of synergy often correlates well with a high rate of therapy failure. A greater knowledge of the mechanisms underlying antibiotic interactions should improve the accuracy of predictions about the in vivo usefulness and safety of drug combinations.