Acute adrenal insufficiency is a rare but life-threatening disorder that develops as a result of inadequate adrenal steroid production. Early diagnosis is key for effective and life-saving treatment of the affected patients. The main clinical features are non-specific, thus often leading to misdiagnosis and invasive diagnostic work up, in particular in patients with previously unknown disease. Adrenal crisis in patients with known chronic adrenal insufficiency is nowadays rare, but can only be prevented by structured patient education on stress-related glucocorticoid dose adjustment. Outcome of adrenal crisis is crucially determined by the physician's clinical competence and immediate initiation of specific treatment.