Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in the ICU and contributes disproportionately to both poor outcomes and the high cost of care in critically ill patients. While VAP has been the focus of extensive research, little consensus exists about methods for diagnosis, treatment, or prevention. Delays in initiating appropriate therapy, antibiotic resistance due to indiscriminate and prolonged use of broad-spectrum antibiotics, and treatment of patients with a low risk of VAP (based on clinical pulmonary infection scores) represent a sample of VAP-related issues that have been addressed in recent clinical trials. Educational programs for VAP prevention and other nonpharmacologic strategies aimed at eliminating VAP have also been explored in clinical investigations. This review highlights selected areas of new clinical research on VAP treatment and prevention in order to place their significance in context.