Diagnosing ventilator-associated pneumonia (VAP) is difficult, creating important clinical dilemmas for intensive care physicians. Adequate empiric antimicrobial therapy is crucial because VAP is associated with increased morbidity and mortality, especially when initial treatment is inappropriate. Because VAP is the most frequent occurring nosocomial infection, it is, to a large extent, responsible for the high antibiotic consumption in ICUs, which is an important cause for selection and induction of antibiotic resistance. In addition, antibiotics may have adverse effects and their costs should be considered. Therefore, a balance should be found between the obvious necessary therapeutic benefits and the negative effects (selection of resistant pathogens, costs, and adverse effects) of antibiotics in the treatment of VAP. Although guidelines for initial antimicrobial therapy have been established, no such recommendations exist for withholding or withdrawing antimicrobial treatment, and little is known about the optimal duration of therapy.