Guidelines published jointly by the American Thoracic Society and Infectious Diseases Society of America endorse the practice of appropriate empirical antibiotic therapy for ventilator-associated pneumonia (VAP) and even provide recommendations for specific antibiotics based on whether a patient has risk factors for multidrug-resistant infections. Unfortunately, the current guidelines provide little insight into how a specific institution can best develop a strategy for providing empirical antibiotic therapy. This review article focuses on important steps that should be taken in developing a hospital-specific pathway for the empirical antibiotic treatment of VAP. Consideration should be given to developing a multidisciplinary group to obtain intensive care unit (ICU)-specific antibiograms for the most common causative organisms, real-time minimum inhibitory concentration (MIC) data or MIC distributions from surveillance studies over a representable time frame, and implementing empirical dosage strategies aimed at achieving not only appropriate therapy but also optimal therapy based on pharmacodynamic targets. A proper deescalation strategy will also be vital to managing antibiotic choices and dosages, as well as providing useful recommendations for discontinuation of therapy. Finally, continued feedback of program results is critical to maintaining compliance as well as for reevaluating empirical antibiotic choices.