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Acinetobacter baumannii-calcoaceticus complex has become a serious nosocomial pathogen due to its persistence in the hospital environment and its broad antimicrobial resistance patterns. This review summarizes the most recent literature pertaining to the clinical management of infections with this bacteria emphasizing in-vitro antimicrobial resistance patterns and antimicrobial efficacy in animals and humans.Although this pathogen can be associated with an elevated crude mortality, it only contributes to this mortality in a subset of high-risk patients. Determining in-vitro activity of antimicrobial agents can be problematic due to conflicting results sometimes obtained through different testing methods. There is no simple answer as to the most appropriate antimicrobial therapy secondary to lack of adequate studies. Imipenem/cilastatin, amikacin, ampicillin/sulbactam, colistin, rifampin, and tetracyclines are typically active against these bacteria. It is also not clear if combination therapy is more effective than monotherapy. In cases in which A. baumannii-calcoaceticus complex bacteria are resistant to all available agents, we have prolonged infusion times, increased drug dose, and altered route of instillation, such as nebulized therapy for pulmonary infections with mixed results. A primary goal of A. baumannii-calcoaceticus complex management should be to prevent initial colonization and subsequent infection by adequate infection control.The A. baumannii-calcoaceticus complex continues to play a significant role in our healthcare systems. Prompt and adequate therapy with agents having in-vitro activity is required once it is established that the bacteria represents infection and not colonization. Aggressive infection control policies should be enforced when this pathogen is identified.