Septic shock is characterized by a relative deficiency in vasopressin, and exogenous administration of arginine vasopressin (AVP) restores vasomotor tone and blood pressure.Thus, AVP is recommended by the Surviving Sepsis Campaign (SSC) as an adjunctive therapy in refractory septic shock. However, the Vasopressin in Septic Shock Trial (VASST), a large randomized con-trolled trial (RCT) that compared AVP with norepineph-rine for the treatment of septic shock, did not find any benefit on mortality. AVP is a mixed agonist of V1a receptor and V2 receptor (V2R), and there is increasing evidence that endothelial V2Rs may aggravate sepsis-induced vasodilatation, fluid accumulation, leukocyte rolling, and microvascular thrombosis. Hence, Rehberg and colleagues evaluated the effects of a selective V2R antagonist in an experimental septic model of ovine fecal peritonitis.