<p>Hypophysitis is defined by inflammation of the pituitary gland and/or infundibulum. It can cause headaches and symptoms due to hypopituitarism. Diagnosis is based on a combination of hormonal and imaging parameters but can, in individuals with an uncertain diagnosis, require a transsphenoidal biopsy. While the risk of immune checkpoint inhibitor-induced hypophysitis is well known, several aetiologies of secondary hypophysitis have been identified and hypophysitis can also occur in relation to pregnancy. Primary hypophysitis is defined by the absence of a secondary cause of hypophysitis. Although each subtype can present with distinct clinical, endocrine and radiological features, extensive overlap makes the aetiological diagnosis difficult. Management of hypophysitis is another challenging task. Whereas some studies have suggested that high-dose glucocorticoids can improve pituitary function and alleviate symptoms, others have found limited benefit. Immunosuppressive agents have also been used as targeted therapy for the underlying condition or in individuals with aggressive hypophysitis, potentially improving both clinical presentation and hormonal function. These therapeutic approaches, used alone or in combination, can be considered in selected patients with primary, pregnancy-related or secondary hypophysitis. The aim of this comprehensive Review is to critically analyse the positive and aetiological diagnostic steps and the management of all subtypes of hypophysitis.</p>