Interventions to prevent pneumonia in the intensive care unit should combine multiple measures targeting the invasive devices, microorganisms and protection of the patient. Microbiological investigation is useful for evaluating the quality of the respiratory sample, and permits early modification of the regimen in light of the microbiological findings. Once pneumonia develops, the appropriateness of the initial antibiotic regimen is a vital determinant of outcome. Three questions should be formulated: (1) is the patient at risk of acquiring methicillin-resistant Staphylococcus aureus, (2) is Acinetobacter baumannii a problem in the institution, and (3) is the patient at risk of acquiring Pseudomonas aeruginosa? Antibiotic therapy should be started immediately and must circumvent any pathogen resistance mechanisms developed after previous antibiotic exposure. Therefore, antibiotic choice should be institution-specific and patient-oriented.