Nosocomial pneumonia (NP) is a difficult diagnosis to establish in the critically ill patient due to the presence of underlying cardiopulmonary disorders (e.g., pulmonary contusion, acute respiratory distress syndrome, atelectasis) and the nonspecific radiographic and clinical signs associated with this infection. Additionally, the classification of NP in the intensive care unit setting has become increasingly complex, as the types of patients who develop NP become more diverse. The occurrence of NP is especially problematic as it is associated with a greater risk of hospital mortality, longer lengths of stay on mechanical ventilation and in the intensive care unit, a greater need for tracheostomy, and significantly increased medical care costs. The adverse effects of NP on healthcare outcomes has increased pressure on clinicians and healthcare systems to prevent this infection, as well as other nosocomial infections that complicate the hospital course of patients with respiratory failure. This manuscript will provide a brief overview of the current approaches for the diagnosis of NP and focus on strategies for prevention. Finally, we will provide some guidance on how standardized or protocolized care of mechanically ventilated patients can reduce the occurrence of and morbidity associated with complications like NP.