A variety of antibiotics, both parenteral and oral, are available to the clinician caring for a child with pneumonia. Although viral pathogens are the common etiologic agents causing community-acquired pneumonia, significant morbidity and mortality exists from disease caused by bacteria and atypical pneumonia agents. Treatment of nosocomial bacterial pneumonia has become particularly difficult with ever-increasing resistance documented in hospital-acquired organisms. This article discusses antibiotic therapy based on clinical presentation and based on identified pathogens, with a discussion of mechanisms of antibiotic resistance and the newer agents that have been designed to meet this continually evolving challenge.