Vasoplegia is a loss of vascular muscle tone which leads to distributive shock by the vasodilation and hypotension. Vasoplegic syndrome (VS) is characterized by hypotension with reduced systemic vascular resistance (SVR) which can lead to hypoperfusion of the organs despite normal or increased cardiac output. It occurs in 9% to 44% of patients after cardiopulmonary bypass surgery. Heart transplantation, burns and sepsis represent some of the clinical factors that can cause vasoplegia. Molecular mechanisms leading to vasoplegia are complex, numerous and not entirely clarified. Inducible nitric oxide synthase (iNOS) which expression in this condition is increased, produces an increased concentration of nitric oxide (NO) in response to inflammatory factors. By increasing the intracellular concentration of cyclic guanosine monophosphate (cGMP), it prevents vasoconstriction which leads to hypotension. Increased NO concentration and decreased vasopressin concentrations by activation of KATP channels result with hyperpolarization of cell membrane that prevents calcium influx through voltage-gated calcium channels. Prostacylins, endothelin-1, hydrogen sulphide, complement components, free radicals, corticosteroids and catecholamine resistance also have the role in aetiology of vasoplegic syndrome. When patients become refractory to noradrenaline and vasopressin, the potential treatment modalities include methylene blue, hydroxycobalamin, hydrocortisone, vitamin C, angiotensin II, α1 agonists and β2 receptor blockers. Further research is needed to find the adequate treatment regimen.