Vasoplegia is defined by hypotension and low systemic vascular resistance despite the normal or elevated cardiac index, a complication frequently following cardiac surgery, carrying high morbidity and mortality rate. Vasoplegia is related with a profound systemic inflammatory response and is mainly mediated by cellular hyperpolarization, a relative vasopressin deficiency, and high levels of inducible nitric oxide, following cardiopulmonary bypass. Cardiopulmonary bypass is a distinct precipitant of vasoplegia, generally due to its association with nitric oxide production and severe vasopressin depletion. Postoperative vasoplegia is usually managed with vasopressors, of which catecholamines are the traditional agents of choice. Recent studies promote the use of non-catecholamine vasopressor (vasopressin) in restoring systemic vascular resistance. Alternative agents are also able to restore vascular tone and improve vasoplegia, including methylene blue, angiotensin II, hydroxocobalamin, and ascorbic acid; however, their effect on patient outcomes is still unclear