Waterhouse–Friderichsen syndrome (WFS) is a clinical conundrum conventionally described as a combination of adrenal hemorrhage, purpura, and shock from an infectious etiology. The first-ever case was reported by Voelcker in 1894. He initially described cases of hemorrhagic smallpox until the autopsy showed bilateral adrenal hemorrhage (Friderichsen, 1955). In 1911, Waterhouse reported a case of a rapidly deteriorating male infant who was later found to have bilateral adrenal hemorrhage on autopsy (Waterhouse, 1911). In 1917 Friderichsen published a report titled “Adrenal apoplexy in children” with a thorough review of the previously published literature. Glanzman in 1933 named the disease Waterhouse–Friderichsen syndrome in honor of the predecessors (Friderichsen, 1955).

In this chapter, we review the etiology, pathogenesis, clinical features, and current practices in the diagnosis and management of WFS.