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In this age of emerging antibiotic resistance, limited therapeutic options exist for treating multidrug-resistant organisms. Combination therapy is commonly employed to manage these infections despite little laboratory guidance as to the efficacy of this approach. Synergy testing methods have been used to assess the interaction of antibiotic combinations in vitro. This review will discuss the four primary methods used to assess synergy, as well as the data that exist for testing of cystic fibrosis. In the final analysis, this review concludes that there is not enough evidence to endorse synergy testing for routine clinical use.