Addison's disease is the manifestation of adrenal glucocorticoid and mineralocorticoid deficiency from T-cell mediated destruction of the adrenal cortex, and is the commonest cause of primary adrenal insufficiency in adults. Due to its vague presentation, diagnosis of Addison's disease is often delayed, and in some cases, individuals present in adrenal crisis. Despite the use of corticosteroid replacement therapy, people with Addison's disease have increased mortality and reduced quality of life. Multiple features are thought to contribute to these outcomes, including inadequacy of adrenal crisis management and the inability of existing therapies to mimic circadian and ultradian rhythms of cortisol release. Current research strategies focus on understanding social and behavioural factors that contribute to adrenal crises, developing therapies that more closely mimic rhythms of physiological cortisol secretion, and developing interventions to restore adrenal steroidogenesis. This Review discusses the clinical features, investigation, and management of Addison's disease.