Adrenal insufficiency may have an insidious onset but can also present as a life-threatening emergency. It is important to recognise the features and perform appropriate investigations to confirm its diagnosis. In developed countries, autoimmune adrenal destruction is the commonest cause of adrenal failure and can be part of Autoimmune Polyglandular Syndromes Types 1 to 4. HLA-DRB1 has been identified as having the strongest association with primary adrenal insufficiency. Modes of inheritance and gene mutations are highlighted for conditions such as autoimmune polyendocrinopathy, congenital adrenal hyperplasia, adrenoleukodystrophy and familial ACTH resistance syndromes. The Synacthen?? test has excellent long-term predictive value and the insulin stress test is the gold standard for diagnosing secondary adrenal insufficiency. Treatment includes glucocorticoid, mineralocorticoid and DHEAS supplements.