The purposes of selective decontamination of the digestive tract are to treat infections that may be incubating at the time a patient is admitted to an intensive care unit (ICU), by intravenous administration of antibiotics during the first days of a stay in the ICU, and to prevent ICU-acquired infections, by topical application of antibiotics in the oropharynx and the gastrointestinal tract. Despite multiple trials in which a considerable reduction in the incidence of ventilator-associated pneumonia was demonstrated, major objections against the routine use of selective decontamination of the digestive tract have included a lack of demonstrated reductions in mortality rates and in length of stay (in individual trials), a lack of cost-efficacy data, and the threat of selection of multidrug-resistant bacteria. Recently, 2 controlled, randomized studies reported significant reductions in mortality rates among patients in ICUs who underwent selective decontamination of the digestive tract in combination with reduced selection of antibiotic-resistant pathogens. However, those studies were performed in settings where levels of antibiotic resistance are low, and some methodological issues remain unresolved. If these beneficial results are confirmed, the question of how to balance these benefits against the expected enhanced selection of methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and, possibly, multidrug-resistant gram-negative bacteria will emerge.