Over the past decade, an increasing prevalence of infections caused by non-fermenting Gram-negative bacteria has been reported in many countries. Among these bacteria, Pseudomonas aeruginosa and Acinetobacter baumannii have been associated with high mortality and treatment failures. Treatment options for multidrug-resistant P. aeruginosa and A. baumannii infections are limited to carbapenems in most cases. The mechanisms of carbapenem resistance have been identified in P. aeruginosa and other Gram-negative non-fermenters, including enzyme production, overexpression of efflux pumps, porin deficiencies, and target- site alterations. This article reviews the in vitro activity of doripenem and compares it with that of imipenem and meropenem against a large collection of non-fermenting Gram-negative bacilli, obtained in worldwide surveillance studies between 2000 and 2010. A detailed examination of the available data demonstrate that doripenem has more potent in vitro antibacterial activity against P. aeruginosa and Acinetobacter species compared to other carbapenems. Furthermore, doripenem has a limited ability to select for carbapenem-resistant mutants in vitro.