Nosocomial lower respiratory tract infections are a common cause of morbidity and mortality in ICU patients receiving mechanical ventilation. Many studies have investigated the management and prevention of ventilator-associated pneumonia (VAP), but few have focused on the role of ventilator-associated tracheobronchitis (VAT). The pathogenesis of lower respiratory tract infections often begins with tracheal colonization that may progress to VAT, and in selected patients to VAP. Since there is no well-established definition of VAT, discrimination between VAT and VAP can be challenging. VAT is a localized disease with clinical signs (fever, leukocytosis, and purulent sputum), microbiologic information (Gram stain with bacteria and leukocytes, with either a positive semiquantitative or a quantitative sputum culture), and the absence of a new infiltrate on chest radiograph. Monitoring endotracheal aspirates has been used to identify and quantify pathogens colonizing the lower airway, to diagnose VAT or VAP, and to initiate early, targeted antibiotic therapy. Recent data suggest that VAT appears to be an important risk factor for VAP and that targeted antibiotic therapy for VAT may be a new paradigm for VAP prevention and better patient outcomes.