Vasoplegic syndrome is an important clinical entity characterized by profound arterial hypotension refractory to vasopressor therapy. The underlying pathophysiology is characterized by a complex and multifactorial dysregulation of both vasodilatory and vasoconstrictive mechanisms. During the last decades, there is growing interest in using methylene blue as an adjunct therapy to treat vasodilatory shock. The present review evaluates the safety and efficacy of methylene blue in cardiac and transplant surgery, severe sepsis and septic shock, severe burn injury, paediatric intensive care, and intoxications. Although most of the currently available evidence reports a benefit in haemodynamic parameters and a decrease in vasopressor requirements following the administration of methylene blue, study designs are heterogeneous, and the overall level of evidence is low. Moreover, a clear and consistent benefit in morbidity and mortality is lacking. Large prospective randomized controlled trials are needed to evaluate the exact role and timing of methylene blue in the treatment of vasopressor refractory vasoplegia.