Risk factors for the development of ventilator-associated pneumonia (VAP), as identified in epidemiological studies, have provided a basis for testable interventions in randomized trials. We describe how these results have influenced patient treatment. Single interventions in patients undergoing intubation have focused on either reducing aspiration of oropharyngeal secretions, modulation of colonization (in either the oropharynx, the stomach, or the whole digestive tract), use of systemic antimicrobial prophylaxis, or ventilator circuit changes. More recently, multiple simultaneously implemented interventions have been used. In general, routine measures to decrease oropharyngeal aspiration and antibiotic-containing prevention strategies appear to be the most effective, and the latter were associated with improved rates of patient survival in recent trials. These benefits must be balanced against the widespread fear of emergence of antibiotic resistance. In hospital settings with low baseline levels of antibiotic resistance, however, the benefits to patient outcome may outweigh this fear of resistance. In settings with high levels of antibiotic resistance, combined approaches of non-antibiotic using strategies and education programs might be most beneficial.