Ventilator-associated pneumonia (VAP) is considered the most frequent infection in the intensive care unit (ICU), although incidence rates depend on the diagnostic methods. Because VAP has been associated with increased mortality and greater costs for medical care, prevention remains an important goal for intensive care medicine. Selective digestive decontamination (SDD), the most frequently studied method of infection prevention, is still controversial despite more than 30 prospective randomized trials and 6 metaanalyses. SDD reduces the incidence of VAP diagnoses, but beneficial effects on duration of ventilation or ICU stay, antibiotic use, and patient survival have not been shown unequivocally. Although recent metaanalyses suggest a 20% to 40% decrease in ICU mortality for SDD used with systemic prophylaxis, this benefit should be confirmed in a large, prospective, randomized study, preferably with a cost-benefit analysis. Selection of pathogens resistant to the antibiotics used in SDD remains the most important drawback of SDD, rendering SDD contraindicated in wards with endemic resistant problems. Other methods of infection prevention that do not create a selective growth advantage for resistant microorganisms may be more useful. Among these are the use of endotracheal tubes with the possibility of continuous aspiration of subglottic secretions, oropharyngeal decontamination with antiseptics, or the semirecumbent treatment position of patients. Although these methods were successful in single studies, more data are needed. Notwithstanding the potential benefits of these interventions, such classic infection control measures as handwashing remain the cornerstone of infection prevention.