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Combination therapy is a common strategy for treatment of multidrug resistant infections. Despite the strong twin rationales of improving efficacy and reducing resistance development, the evidence supporting this strategy remains controversial. The aims of this review are to assess the most recent studies supporting the use of combination therapy for treating infections because of carbapenem-resistant Enterobacteriaceae (CRE) and to highlight relevant areas for further research.Evidence supporting the use of combination therapy for the treatment of CRE remains limited to in-vitro experiments and observational studies with considerable risk of bias. Very few antibiotic combinations have been tested in well designed randomized controlled trials, making it difficult to draw general conclusions for clinical practice.Further studies are urgently needed to test the most promising synergistic combinations. New drugs potentially active against CRE should also to be tested in studies with adequate sample size and truly representative of the general patient population.