Sepsis is a systemic inflammatory response syndrome (SIRS) caused by infection, and it is one of the major causes of mortality of critical care patients. Since it has been reported that early, optimal treatment of patients is important to reduce mortality from sepsis, a sepsis marker with a high sensitivity and specificity is required. Presepsin (P-SEP) was discovered as a new marker whose levels elevated specifically in the blood of patients with sepsis in Japan in 2002. Presepsin is a 13-kDa glycoprotein that is a truncated N-terminal fragment of CD14. Since one of the production mechanisms of presepsin is related to the phagocytosis of bacteria, the biological characteristics of presepsin are different from those of other inflammatory markers. Presepsin has three features in comparison with procalcitonin(PCT), C-reactive protein(CRP), and interleukin-6 (IL-6): 1) Presepsin can be detected earlier after the onset of infection; 2) Presepsin is not affected by severe trauma, severe burn, or invasive surgical procedures, which lead to SIRS, more than PCT, CRP, or IL-6; 3) Presepsin levels reflect the clinical condition of septic patients. Although clinical evidence is not sufficient at present, presepsin may be a strong tool for the development of novel treatment strategies for sepsis.