Methylene blue has been in medicinal use for centuries and is best known as an antidotal treatment for acquired methemoglobinemia (MetHB). More recently, methylene blue has gained recognition for its efficacious use in the treatment of ifosfamide neurotoxicity and refractory vasoplegic shock in both the pediatric and adult critical care literature, extending its use beyond MetHB. Methylene blue's mechanism of action is somewhat complex and based partly on its oxidizing capabilities, ironically the same mechanism that causes MetHB. This review will examine methylene blue's use in the treatment of acquired MetHB and ifosfamide neurotoxicity and review the current literature regarding its role in critically ill pediatric and adult patients with refractory vasoplegic shock. Methylene blue's pharmacologic actions, dosing, and adverse effects will also be discussed.