Ventilator-associated pneumonia (VAP) is defined as a nosocomial pneumonia occurring > 48 h after endotracheal intubation. VAP may occur very early after intubation and it is usually defined as early-onset pneumonia, which occurs during the first 4 days. The occurrence of VAP is associated with an increase in morbidity and mortality. The pathogenesis of VAP often results from aspiration of colonised secretions in injured patients and this colonisation of the upper airway acts as a main risk factor in the development of pneumonia. It has been hypothesised that the bacterial inoculum may be decreased through the administration of systemic antibiotic prophylaxis. Antibiotic prophylaxis strategies to prevent VAP can be administered over an extended period to cover all microorganisms using selective digestive decontamination regimens, or in a short-term course of no more than 24 h. Probably, the second strategy is the most useful in the prevention of VAP because it has a lower impact on the emergence of bacterial resistance. This manuscript aims to review current opinions regarding antibiotic prophylaxis strategies in the prevention of VAP.