Ventilator-associated pneumonia (VAP) is the most frequent life-threatening nosocomial infection in intensive care units. The diagnostic is difficult because radiological and clinical signs are inaccurate and could be associated with various respiratory diseases. The concept of infection-related ventilator-associated complication has been proposed as a surrogate of VAP to be used as a benchmark indicator of quality of care. Indeed, bundles of prevention measures are effective in decreasing the VAP rate. In case of VAP suspicion, respiratory secretions must be collected for bacteriological secretions before any new antimicrobials. Quantitative distal bacteriological exams may be preferable for a more reliable diagnosis and therefore a more appropriate use antimicrobials. To improve the prognosis, the treatment should be adequate as soon as possible but should avoid unnecessary broad-spectrum antimicrobials to limit antibiotic selection pressure. For empiric treatments, the selection of antimicrobials should consider the local prevalence of microorganisms along with their associated susceptibility profiles. Critically ill patients require high dosages of antimicrobials and more specifically continuous or prolonged infusions for beta-lactams. After patient stabilization, antimicrobials should be maintained for 7–8 days. The evaluation of VAP treatment based on 28-day mortality is being challenged by regulatory agencies, which are working on alternative surrogate endpoints and on trial design optimization.