Ventilator-associated pneumonia (VAP) management depends on the interaction between the infective agent, the host response, and the antimicrobial drug used. After the pathogen reaches the lungs, two outcomes are possible: either the microorganisms are eliminated by the host immune system, or they overcome the immune system and cause pulmonary infection. When a patient is thought to have VAP, two steps are strongly recommended: etiologic diagnostic testing and the immediate initiation of antibiotics. The daily management of VAP remains a challenge for physicians in the ICU. In recent years, a more dynamic approach has evolved, updating local epidemiology, evaluating VAP and diagnostic tools every day, and assessing host response using clinical and biochemical parameters.