Ventilator-associated pneumonia is a frequent cause of ICU-acquired infections. These infections are associated with high morbidity and mortality. The increase in antibiotic resistance, particularly among Gram-negative bacilli, makes the choice of empiric antibiotic therapy complex for physicians. Multidrug-resistant organisms (MDROs) related infections are associated with a high risk of initial therapeutic inadequacy. It is, therefore, necessary to quickly identify the bacterial species involved and their susceptibility to antibiotics. New diagnostic tools have recently been commercialized to assist in the management of these infections. Moreover, the recent enrichment of the therapeutic arsenal effective on Gram-negative bacilli raises the question of their place in the therapeutic management of these infections. Most national and international guidelines recommend limiting their use to microbiologically documented infections. However, many clinical situations and, in particular, the knowledge of digestive or respiratory carriage by MDROs should lead to the discussion of the use of these new molecules, especially the new combinations with beta-lactamase inhibitors in empirical therapy. In this review, we present the current epidemiological data, particularly in terms of MDRO, as well as the clinical and microbiological elements that may be taken into account in the discussion of empirical antibiotic therapy for patients managed for ventilator-associated pneumonia.