Ventilator-associated pneumonia (VAP), a major cause of ICU infection, results in high morbidity, mortality, and health-care costs. Multiple risk factors for VAP involve complex host factors and ubiquitous pathogens that require several different types of prevention strategies. Prevention efforts should focus on reducing bacterial colonization, and limiting aspiration, antibiotic exposure, and use of invasive devices. Although evidence-based prevention guidelines are available, they are lengthy, often ignored, and not implemented. New insights into the barriers to implementation of effective prevention programs are emerging. This article provides highlights from recent guidelines and publications discussing VAP prevention strategies and examines barriers to their implementation. Prevention and implementation of cost-effective strategies to reduce risk and improve patient outcomes should be prioritized. Clearly, prevention programs should be population specific and may vary among hospitals, but a multidisciplinary prevention team led by a “champion” is recommended to help set priorities, benchmarking goals, analyze data, and sow the seeds of change for risk reduction.