Despite efforts to improve treatment outcomes, mortality in septic shock remains high. In some patients, despite the use of several adrenergic drugs, features of refractory vasoplegic shock with progressive multiorgan failure are observed. We present a case report of the successful reversal of vasoplegic shock following the use of methylene blue, a selective inhibitor of the inducible form of nitric oxide synthase, which prevents vasodilation in response to inflammatory cytokines. We also briefly review the literature.