Sepsis remains one of the leading causes of mortality in the United States. Cardiovascular compromise is one of the major contributors to the high mortality associated with sepsis. Current cardiovascular support in patients with septic shock involves fluid administration, use of catecholamines, and potentially the use of inotropes, corticosteroids, or arginine vasopressin. Vasopressin is an endogenous hormone essential for both osmotic and cardiovascular homeostasis. Various studies have suggested that exogenous administration of arginine vasopressin may be an effective adjunctive therapy to traditional catecholamines for the management of hypotension during septic shock. Of particular interest is the Vasopressin and Septic Shock Trial (VASST), which found no mortality benefit when comparing the addition of arginine vasopressin to norepinephrine versus continuous dose increases in norepinephrine alone. However, results of the a priori subgroup and post hoc analyses of this trial suggest that patients may benefit if arginine vasopressin is used in patients with less severe shock, defined as those receiving a relatively low norepinephrine-equivalent dose of 5-14 μg/minute, or in those at risk for renal failure. Current guidelines from the Surviving Sepsis Campaign recommend arginine vasopressin 0.03 unit/minute may be added to norepinephrine with the anticipation of an effect equal to higher doses of norepinephrine alone. Many practitioners continue to utilize arginine vasopressin for patients with septic shock due to its mechanisms of benefit on pathophysiologic derangements in this disease. Clinicians must be knowledgeable about the use of arginine vasopressin in septic shock, including controversial areas where guidelines do not always provide concrete recommendations.