Ventilator-associated pneumonia is the most frequent intensive care unit (ICU)-related infection in patients requiring mechanical ventilation. In contrast to other ICU-related infections, which have a low mortality rate, the mortality rate for ventilator-associated pneumonia ranges from 20% to 50%. These clinically significant infections prolong duration of mechanical ventilation and ICU length of stay, underscoring the financial burden these infections impose on the health care system. The causes of ventilator-associated pneumonia are varied and differ across different patient populations and different types of ICUs. This varied presentation underscores the need for the intensivist treating the patient with ventilator-associated pneumonia to have a clear knowledge of the ambient microbiologic flora in their ICU. Prevention of this disease process is of paramount importance and requires a multifaceted approach. Once a diagnosis of ventilator-associated pneumonia is suspected, early broad-spectrum antibiotic administration decreases morbidity and mortality and should be based on knowledge of the sensitivities of common infecting organisms in the ICU. De-escalation of therapy, once final culture results are available, is necessary to minimize development of resistant pathogens. Duration of therapy should be based on the patient's clinical response, and every effort should be made to minimize duration of therapy, thus further minimizing the risk of resistance.