Ventilator-associated pneumonia (VAP) is the most frequent intensive care unit (ICU)-acquired infection among patients receiving mechanical ventilation. Consensus, however, on the most appropriate diagnostic strategy for patients clinically suspected of having developed VAP has yet to be reached. Concern about the inaccuracy of clinical approaches to VAP recognition and potential for excessive use of antibiotics in the ICU had led numerous investigators to postulate that quantitative cultures of specimens obtained with bronchoscopic or nonbronchoscopic techniques, such as bronchoalveolar lavage (BAL) and/or protected specimen brush (PSB), could improve identification of patients with true VAP and facilitate decisions whether to treat. Other than decision-analysis studies and one retrospective study, only five trials assessed the impact of such a quantitative bacteriological strategy on antibiotic use and outcome of patients suspected of VAP using a randomized scheme. In one study, the invasive management strategy was significantly associated with earlier attenuation of organ dysfunction and less antibiotic exposure, but the four other trials could not replicate these positive findings, including a large Canadian study that enrolled 740 patients. Because antibiotics were continued in most patients with negative BAL cultures in contradiction with the bacteriological algorithm, additional studies will be needed before concluding that a strategy based on the systematic collection of distal pulmonary secretions before introduction of new antibiotics and quantitative culture techniques is useless and cannot prevent the overuse of antimicrobial agents in the ICU.