Sepsis is a serious condition with high morbidity and mortality for which clinical diagnostic criteria lack sensitivity and specificity. Early initiation of appropriate antibiotics and goal-directed therapies reduces mortality. Conversely, overuse and misuse of antibiotics, including continuing antibiotics longer than necessary for cure, can result in adverse events and add to the increasing problem of antibiotic resistance. Although critically ill patients in the intensive care units (ICUs) have higher morbidity and mortality rates, the same issues are also relevant to other clinical conditions, including neonatal sepsis, febrile illness in children, pneumonia, and other respiratory tract infections with respect to the initiation, duration, or change in antibiotic therapy. Again, the duration of antibiotic therapy is often undefined, and clinical features are of limited help in guiding discontinuation of therapy. Several serum biomarkers have been identified in recent years that have the potential to help diagnose local and systemic infections, differentiate bacterial and fungal infections from viral syndromes or noninfectious conditions, prognosticate, and ultimately guide management, particularly of antibiotic therapy. Among these, procalcitonin is the most extensively studied biomarker. Numerous studies have investigated the potential roles of procalcitonin in diagnosing and managing local and systemic infections. There is some evidence that procalcitonin is more specific for bacterial infections, with serum levels rising at the onset of infection and falling rapidly as the infection resolves, as compared with other markers. However, its clinical utility in diagnosing and managing patients with suspected infections remains unclear. The objective of this systematic review was to synthesize comparative studies examining the various uses of procalcitonin in the clinical management of patients with suspected local or systemic infection. The patient populations included critically ill adults with suspected sepsis or other serious bacterial infections, neonates with suspected early neonatal sepsis, patients with upper and lower respiratory tract infections, children with fever of unknown source, and postoperative patients with infections. Initial review of the literature during topic development and topic refinement suggested that the most common use for procalcitonin-guided management was in decisionmaking related to the initiation or discontinuation of antibiotic therapy in these various populations. This led us to construct an analytical framework that focused on the following Key Question. Key Question: In selected populations of patients with suspected local or systemic infection, what are the effects of using procalcitonin measurement plus clinical criteria for infection to guide initiation, discontinuation, or a change of antibiotic therapy when compared with clinical criteria for infection alone on: Intermediate outcomes, such as initiation, discontinuation, or change of antibiotic therapy; antibiotic use; and length of stay? Health outcomes, such as morbidity, mortality, function, quality of life, and adverse events of antibiotic therapy (persistent or recurrent infection, and antibiotic resistance)?