Septic shock remains one of the major causes of morbidity and mortality in the critically ill. Despite early goal therapy and administration of cathecholaminergic agents, up to 30% of patients succumb to the disease. In this manuscript, we first summarize the standard of care of patients with septic shock and current guidelines. We review the physiologic role of vasopressin and its role in septic shock management. We then review the most up-to-date evidence on the potential role of V1a receptor agonists such as Selepressin, in septic shock. Exciting new trials are being completed in order to elucidate the role of V1a receptor agonists as potential first-line vasopressor alternatives in the therapy of circulatory shock in septic patients.