Partial or complete deficiency of anterior or posterior pituitary hormone production leads to central hypoadrenalism, central hypothyroidism, hypogonadotropic hypogonadism, growth hormone deficiency, or arginine vasopressin deficiency depending on the hormones affected. Hypopituitarism is rare and likely to be underdiagnosed, with an unknown but rising incidence and prevalence. The most common cause is compressive growth or ablation of a pituitary or hypothalamic mass. Less common causes include genetic mutations, hypophysitis (especially in the context of cancer immunotherapy), infiltrative and infectious disease, and traumatic brain injury. Clinical features vary with timing of onset, cause, and number of pituitary axes disrupted. Diagnosis requires measurement of basal circulating hormone concentrations and confirmatory hormone stimulation testing as needed. Treatment is aimed at replacement of deficient hormones. Increased mortality might persist despite treatment, particularly in younger patients, females, and those with arginine vasopressin deficiency. Patients with complex diagnoses, pregnant patients, and adolescent pituitary-deficient patients transitioning to adulthood should ideally be managed at a pituitary tumour centre of excellence.