Critically ill patients are frequently at risk of sepsis or inflammatory conditions. Procalcitonin (PCT) is a biomarker for critically ill patients to differentiate sepsis from non-infectious triggers of the systemic inflammatory response syndrome. It has been recently shown that PCT is a valuable tool to guide antibiotic treatment in patients with bacteria infections. However, PCT is also less than a universal and perfect biomarker, and its physiologic role remains unknown. An increase in PCT is associated not only with localized bacterial infection, but also with non-infectious disease or other microbial infections. Numerous studies have suggested that use of PCT would reduce patients' exposure to antibiotics; however, the use of PCT-guided management of antibiotics strategy needs further study to validate their safety in daily practice in ICU settings. Data supporting this concept from randomized trials are still required. Future studies should focus on PCT kinetics. On the other hand, the need for biologic role of PCT shall be highlighted. Immunoneutralization of PCT will likely be a therapeutic approach for human sepsis only if its physiologic effects are elaborated. The aim of this review is to summarize and discuss the current evidence for PCT in a series of clinical settings.