Acinetobacter baumannii is a highly resilient, gram-negative coccobacillus that thrives within the unique and complex ecological setting of an intensive care unit. This evolving pathogen has now surpassed human capacity to create new antimicrobials, and has led physicians into a concerning era for hospital-acquired infections. This review presents the available evidence on the therapeutic strategies for A. baumannii infection, with a particular focus on clinical human data. The utility of existing and older antimicrobials such as sulbactam and the polymyxins are explored, as well as, the potential role of newer agents such as tigecycline. Other important adjunctive strategies such as pharmacodynamic target attainment and infection control implementation are briefly discussed. It is now clear that new antimicrobials with unique mechanisms of action are urgently required to combat the rising trends seen globally with drug-resistant A. baumannii.