Ventilator-associated pneumonia is a significant contributor to excess morbidity and mortality in the ICU. Alteration of physical defenses, bacterial flora, and immune response contribute to the susceptibility of the critically ill ventilated patient. Controversies regarding its definition continue to complicate the understanding of the extent of the disease and evaluation of the outcome of therapies. Traditional parameters, such as clinical suspicion with standard tracheal aspirates, are associated with overuse of antibiotics, a prime risk factor for development of resistant organisms and increased mortality. Global emergence of resistance is also a major concern. Whether invasive methods have any substantial clinical benefit either through improved patient outcomes or lower rates of resistance remains to be proved. In patients who fail to respond to therapy, a search for nonpulmonary infections and noninfectious causes of pulmonary infiltrates is essential. Finally, preventative measures offer additional areas of investigation that could favorably impact on the incidence of infection.