Background: Tumor necrosis factor related apoptosis induced ligand, TRAIL is a new proapoptotic member of TNF superfamily which has been implicated in the regulation of apoptosis of tumor cell when bind to its receptor DR4/DR5. Objective: To summarize the potential mechanism of TRAIL in the pathophysiology of sepsis. Content: Based on research using sepsis models, we concluded that TRAIL could accelerate the apoptosis of activated neutrophil and this molecular was involved in the immunosupression. Trend: Studies about TRAIL involved a variety of disciplines such as tumor therapy, autoimmune disease, cardiovascular disease, transplant, infections, trauma and so on. TRAIL played an important role in the regulation of immune response of septic host.