Validation of guidelines for the management of hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) is important to confirm the reliability of such guidelines in clinical practice and to ascertain their impact on patient-outcome parameters. In order to improve outcomes, guidelines need to be adapted to the local microbiology, accurately predict pathogens, and help physicians to administer the most appropriate empiric antimicrobial therapy. Overall, the implementation of guidelines is followed by an increase in the initially adequate antibiotic treatment. Rather than the onset with time, a proper identification of risk factors for specific pathogens is crucial in choosing an appropriate empiric treatment and needs to be addressed in future guidelines. However, only a few studies have demonstrated that the prediction of microorganisms by HAP and VAP guidelines is reliable. Guideline validation studies are not easy and have to take into account different variables, potentially related with the outcome of patients.