Multidrug-resistant Acinetobacter spp. are emerging nosocomial pathogens and have become a leading cause of Gram-negative infections in many parts of the world. Acinetobacter spp. are commonly implicated in bloodstream infection, hospital-acquired pneumonia, and wound and other surgical-site infections. They are difficult to treat, thus often leading to adverse patient outcome. Group II carbapenems (imipenem/cilastatin and meropenem) are the agents of choice for the treatment of severe infections caused by Acinetobacter spp. isolates susceptible to this antimicrobial group, but infection with carbapenem-resistant strains is increasingly encountered. Therapy of such infections necessitates the use of old drugs (e.g. colistin), unusual drugs (e.g. sulbactam) or drugs with which there is presently little clinical experience (e.g. tigecycline). Case reports, case series and small comparative observational studies suggest that these regimens are efficacious and demonstrate lower-than-expected toxicity, but there is substantial variation between these reports. Combination antimicrobial therapy is often used to treat infections caused by such multidrug-resistant strains. This article summarizes the cumulative experience with and the evidence for treating infections caused by multidrug-resistant Acinetobacter spp. infections. Special emphasis is placed on the use of 'non-traditional' antimicrobial agents, various aspects of combination therapy, alternative routes of drug administration, and discrete entities such as ventilator-associated pneumonia and postsurgical meningitis.