Pneumonia, including community-acquired bacterial pneumonia, hospital-acquired bacterial pneumonia, and ventilator-acquired bacterial pneumonia, carries unacceptably high morbidity and mortality. Despite advances in antimicrobial therapy, emergence of multidrug resistance and high rates of treatment failure have made optimization of antibiotic efficacy a priority. This review focuses on pharmacokinetic and pharmacodynamic approaches to antibacterial optimization within the lung environment and in the setting of critical illness. Strategies for including these approaches in drug development programs as well as clinical practice are described and reviewed.