Infections associated with Acinetobacter baumanni has been increasingly observed around the globe with the rapid emergence and high prevalence of multidrug resistance or pan-resistance in this bacterial species. A. baumanii itself displays significant intrinsic resistance owning to the interplay between the outer membrane permeability barrier and active drug efflux pumps. Most mechanisms of resistance occurred in bacteria have been identified in A. baumannni with the predominant observations either in the chromosome or on plasmids of the clusters of multidrug resistance genes and mobile genetic elements such as tranposons and integrons, which are responsible for the unusual high-levels of acquired multidrug resistance and also result in the very limited drug options for the anti-infective therapy. Although carbapenems, sulbactam-containing antibiotic combinations, colistin or other antibiotic combination therapy may be selected for therapy of A. baumanni infections, the clinical efficacy of these drug regimens remains to be observed closely and if needed, the drug selection should be adjusted by taking into account of the antibiotic susceptibility testing. Despite some newer antibiotics including tigecycline display anti-Acinetobacter activity in vitro, their clinical efficacy remains to be further studied. Effective risk management for nosocomial infection control including the prudent use of antibiotics is a key in preventing or reducing the infections by A. baumanni as well as their emergence and persistence of drug resistance.