Ventilator-associated pneumonia (VAP) continues to complicate the course of 8 to 28% of patients receiving mechanical ventilation (MV). In contrast to infections of more frequently involved organs (e.g., urinary tract and skin), for which mortality is low, ranging from 1 to 4%, the mortality rate for VAP ranges from 24 to 50% and can reach 76% in some specific settings or when lung infection is caused by high-risk pathogens. The predominant organisms responsible for infection are Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacteriaceae, but etiologic agents widely differ according to the population of patients in an intensive care unit, duration of hospital stay, and prior antimicrobial therapy. Because appropriate antimicrobial treatment of patients with VAP significantly improves outcome, more rapid identification of infected patients and accurate selection of antimicrobial agents represent important clinical goals. 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. When fiberoptic bronchoscopy is not available to physicians treating patients clinically suspected of having VAP, we recommend using either a simplified nonbronchoscopic diagnostic procedure or following a strategy in which decisions regarding antibiotic therapy are based on a clinical score constructed from seven variables. Selection of the initial antimicrobial therapy should be based on predominant flora responsible for VAP at each institution, clinical setting, information provided by direct examination of pulmonary secretions, and intrinsic antibacterial activities of antimicrobial agents and their pharmacokinetic characteristics. Further trials will be needed to clarify the optimal duration of treatment and the circumstances in which monotherapy can be safely used.