We sought to control infection due to multidrug-resistant Acinetobacter baumannii (MDR-Ab) by identifying isolates as clonally related, leading to enhanced infection-control measures, including cohorting, surveillance, contact precaution, initial therapy with ampicillin/sulbactam and local polymyxin B, and, more recently, therapy with synergistic antibiotic combinations. Class restriction of cephalosporins has been associated with a reduction in cephalosporins-cephamycin-carbapenem resistance among nosocomial Klebsiella isolates. This has been supplemented by restriction of carbapenem use after an initial 24-h period in an effort to reduce the selection of porin-deficient, carbapenem-resistant A. baumannii and Pseudomonas aeruginosa. Evidence is reviewed suggesting that eradication of MDR-Ab nosocomial colonization may prevent subsequent infection. Relatively few standard antibacterial drugs remain active against MDR-Ab. Published clinical results of therapy with these agents are reviewed, and in vitro evidence of synergy between them is presented that suggests that combination therapy should be studied for enhanced clinical activity.