Glucocorticoids are highly effective medicines in the treatment of inflammatory disorders. However they cause severe dose-related adverse reactions, particularly where taken systemically for prolonged periods. Systemic glucocorticoids are therefore given at dosage sufficient to control the disease, then withdrawn as fast as is possible to minimise dose-related adverse effects without losing disease control. End-of-use adverse reactions present a major challenge in the withdrawal of long term (>3 weeks) glucocorticoids. Suppression of the hypothalamic-pituitary-adrenal (HPA) axis causes adrenal insufficiency, which is potentially life threatening and can become symptomatic as treatment is withdrawn. Adrenal insufficiency can be extremely difficult to differentiate from ‘glucocorticoid withdrawal syndrome’, where patients experience symptoms despite adequate adrenal function, and from psychological dependence. Long term systemic glucocorticoids should therefore be withdrawn slowly. The rate at which the dose is tapered should initially be determined by treatment requirements of the underlying disease. Once physiological doses (prednisolone 7.5mg or equivalent) are reached, the rate of reduction is determined by rate of HPA recovery and need for exogenous glucocorticoid cover while endogenous secretion recovers. If symptoms prevent treatment withdrawal, HPA testing should be used to look for adrenal insufficiency. Patients with adrenal insufficiency require physiological doses of glucocorticoids for adrenal replacement, which may be lifelong if the HPA axis fails to recover.