Nosocomial pneumonia carries a high morbidity and mortality and creates a large burden on health care use. As resistance to currently available antibiotics continues to increase, the role of pharmacodynamics in drug regimen optimization becomes pivotal to the clinical success of patient therapy. This article reviews the evidence behind pharmacodynamic optimization including the use of Monte Carlo simulations, changes in pharmacokinetic parameters of critically ill patients, and differing strategies to optimize drug regimens. Emphasis is placed on drugs used to treat hospital-acquired and ventilator-acquired pneumonia, and programs implementing pharmacodynamic optimization are highlighted.