The optimal management strategy for ventilator-dependent patients who develop symptoms suggestive of lung infection remains controversial. Our personal bias is that using bronchoscopic techniques to obtain protected-brush and bronchoalveolar lavage specimens from the affected area in the lung permits physicians to devise a therapeutic strategy that is superior to one based only on clinical evaluation. These bronchoscopic techniques, when they are performed before new antibiotics are administered, enable physicians to identify most patients who need immediate treatment and to select optimal therapy, in a form that is safe and well tolerated by patients. Furthermore, they frequently permit physicians to withhold antimicrobial treatment from patients without infection, thereby minimizing the risk of emergence of resistant microorganisms in the intensive care unit. Despite many advances in antimicrobial therapy, successful treatment of patients with nosocomial pneumonia remains a complex undertaking, and ultimately further trials will be needed to clarify the optimal duration of treatment and the circumstances in which monotherapy can be safely used.