Ventilator-associated pneumonia (VAP) is a well-known complication of invasive mechanical ventilation in critically ill patients. The presence of an endotracheal tube (ETT) is one of the major culprits for VAP development: air flow moves pathogens toward the distal airways, while clearance of the trachea is blunted due to reduced tracheal ciliary movement and impaired cough. Several measures are recognized as being useful to prevent VAP, and these are usually grouped in a VAP bundle (ie, avoiding intubation or re-intubation whenever possible; head of bed elevation; hand hygiene; shortening ventilation through sedation interruptions, spontaneous breathing trials, or thromboembolic prophylaxis). However, other interventions have been proposed to reduce VAP rate; some of these interventions have been reported in large clinical trials to be effective, some have been evaluated in small observational studies, and still others at a pre-clinical stage. Some strategies aim to improve the ETT design via a subglottic drainage system, with treatment of the ETT surface to reduce pathogen activity, or by modification of the cuff shape or cuff material to provide a better seal. Another proposed strategy is improving airway care through control of cuff pressure, cleaning the ETT, or use of closed suction systems. Other interventions target a patient's position in the bed to reduce aspiration of digestive content in the airways, or the use of probiotics to modulate gastric flora. Some of these measures are supported by strong evidence, but the impact on relevant outcomes such as duration of ventilation or mortality, as well as cost-benefit ratio, is still unclear, resulting in lack of widespread use.