Ventilator-associated pneumonia (VAP) is the most frequent infection in the intensive care unit. The importance of this entity lies not only in its high incidence but also in the significant mortality it produces. Therefore, a new episode of VAP should be clinically suspected when new or persistent radiological opacity, purulent respiratory secretions and other signs of sepsis (fever and leukocytosis) are present. In these patients, at the very least, tracheal aspirate samples with quantitative culture and direct staining should be immediately obtained, followed by prompt initiation of empirical broad-spectrum antibiotic therapy. The choice of initial antibiotic therapy should be patient-based, taking into account the risk factors associated especially with VAP caused by Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus, because of the high associated mortality. To evaluate resolution of VAP, we analyze various clinical variables (based mainly on resolution of fever and hypoxemia) and microbiologic information. Once the microorganism responsible for VAP has been isolated, antibiotic therapy can be adapted, based on de-escalation, to reduce the emergence of resistant bacteria. Recent studies suggest that shorter antibiotic regimens reduce the emergence of antibiotic-resistant pathogens, cost and adverse events.