Nosocomial pneumonia remains a common complication in patients treated with endotracheal intubation and mechanical ventilation and continues to have a significant impact on the mortality rate of these patients. Epidemiologic studies have shown that the risk of pneumonia increases with the duration of intubation but that the period of highest risk is the first 2 weeks of therapy. Gram-negative bacteria account for most nosocomial pneumonias in intubated patients, but Staphylococcus aureus may also play a role in what may be a polymicrobial infection. In the most seriously ill individuals, and in those treated with long-term mechanical ventilation, Pseudomonas aeruginosa is a common pathogen. Endotracheal intubation and mechanical ventilation predispose to pneumonia for a variety of reasons (see Fig. 1). The endotracheal tube can have direct effects on the airway that result in a reduction in local host defenses. Thus, mucosal injury can reduce mucociliary function, while upper airway defenses are bypassed and the effectiveness of cough is reduced. Indirectly, intubation can result in an enhanced capacity of tracheobronchial cells to bind gram-negative bacteria, an effect that favors airway colonization and pneumonia. The injury to the airway can create binding sites for bacteria in the basement membrane of the bronchial tree and the stimulation of the secretion of mucus, which then stagnates and can create potential sites for bacterial adherence. The endotracheal tube also enhances bacterial entry to the lung by serving as a reservoir for bacteria to remain sequestered, safe from host defenses. Respiratory therapy devices can allow bacteria to proliferate and can then introduce them into the patient if not handled properly. Finally, patients who are ill enough to require intubation also have disease-associated impairments in systemic host defense, which add to the impairments caused by the use of an artificial airway. The host defense impairments that occur in mechanically ventilated patients can lead to respiratory tract infection in the form of either febrile tracheobronchitis or pneumonia. The diagnosis of pneumonia in intubated patients is difficult and controversial. It can be made by either clinical criteria or microbiologic criteria, the latter by using a bronchoscopically directed protected specimen brush. Therapy of pneumonia in mechanically ventilated patients is not always successful, and systemic antibiotics may need to be supplemented by topical antimicrobials. No clearly effective prophylactic strategy currently exists, but our understanding of pneumonia pathogenesis has led to some promising directions. As more data are collected, inhaled antibiotics, selective digestive decontamination, and enhancement of host defenses by cytokines and pre-formed antibodies may emerge as useful approaches.