Curbing antibiotic resistance is a challenge in health care today. Infections caused by multidrug-resistant organisms are estimated to cause 12,000 deaths and cost 3.5 billion dollars in excess health care costs in the United States annually. This article focuses on relevant infection control measures for vancomycin-resistant enterococci, multidrug-resistant gram-negative infections, and Clostridium difficile. Common control strategies targeting these pathogens are reviewed and opportunities for research and more effective deployment of existing tools are highlighted. When there is less extensive evidence available from the published literature, the experience with methicillin-resistant Staphylococcus aureus is discussed as it might apply to other pathogens.