Vasopressin is a potent vasopressor for improving organ perfusion during septic shock. The rationale for the use of vasopressin is its relative deficiency of plasma levels and hypersensitivity to its vasopressor effects during septic shock. Growing evidence suggests that low-dose (<0.04 U/min) vasopressin is safe and effective for the treatment of vasodilatory shock. Although it is being used more frequently, there are no randomized clinical trials comparing vasopressin as a first-line agent to commonly used vasopressors. However, vasopressin causes arterial smooth muscle cell contraction through a non-catecholamine receptor pathway, thus it represents an attractive adjunct to the management of septic shock, especially when catecholamines are ineffective.