Acinetobacter species are widespread environmental, nonfermentative, aerobic, gram-negative coccobacilli. Most infections due to this organism are opportunistic in nature and occur in patients who spend extended time in the intensive care unit (ICU) due to severe underlying disease, and who need prolonged therapy with mechanical ventilation and antimicrobial agents. Because the only factor amenable to prevention in this setting is antimicrobial therapy, avoidance of unnecessary antibiotics should be a high priority in management of such patients. Nosocomial spread of A. baumannii in the ICU setting has often been attributed to ventilatory equipment and to colonized nursing and respiratory personnel via hand transmission. In fact, the epidemiology of nosocomial respiratory colonization and/or infection with A. baumannii is now commonly much more complex due to the coexistence of epidemic cases with unrelated sporadic cases caused by different strains. This underscores the necessity to use molecular typing to improve the detection of microepidemics amenable to early control. Crude mortality rates of 30 to 75% have been reported for nosocomial infection due to Acinetobacter species, with the highest rates reported in ventilator-dependent patients. As with many other opportunistic gram-negative bacilli, increasing antibiotic resistance has hindered the therapeutic management of nosocomial infection due to Acinetobacter species. A. baumannii are now frequently resistant to most available antibacterial drugs, with some centers reporting up to 80% of strains resistant to all aminoglycosides. Even resistance to imipenem, which was for several years the most effective drug in treating Acinetobacter nosocomial infections, has now been described in several reports. Unfortunately, the unique propensity of Acinetobacter species to develop resistance to multiple antimicrobial agents reinforces concerns about the imminence of a post-antimicrobial era where no effective antibiotics will be available to treat this type of infection.