Adrenal insufficiency, primarily presenting as an adrenal crisis, is a life-threatening emergency and requires prompt therapeutic management including fluid resuscitation and stress dose hydrocortisone administration. Primary adrenal insufficiency is most frequently caused by autoimmune adrenalitis, and hypothalamic-pituitary tumors represent the most frequent cause of secondary adrenal insufficiency. However, the exact underlying diagnosis needs to be confirmed by a stepwise diagnostic approach, with an open eye for other differential diagnostic possibilities. Chronic replacement therapy with glucocorticoids and, in primary adrenal insufficiency, mineralocorticoids requires careful monitoring. However, current replacement strategies still require optimization as evidenced by recent studies demonstrating significantly impaired subjective health status and increased mortality in patients with primary and secondary adrenal insufficiency. Future studies will have to explore the potential of dehydroepiandrosterone replacement and modified delayed-release hydrocortisone to improve the prospects of patients with adrenal insufficiency.