Isolation or cohorting of infected patients is an old concept. Its purpose is to prevent the transmission of microorganisms from infected or colonized patients to other patients, hospital visitors, and health care workers, who may subsequently transmit them to other patients or become infected or colonized themselves. Because the process of isolating patients is expensive, time-consuming, often uncomfortable for patients and may impede care, it should be implemented only when necessary. Conversely, failure to isolate a patient with multidrug-resistant microorganisms may lead to adverse outcomes, and may ultimately be expensive when one considers the direct costs of an outbreak investigation and the indirect costs of lost productivity. In this review, we argue that contact precautions are essential to control the spread of epidemic and endemic multidrug-resistant microorganisms, and discuss limitations of some available data.