Hypophysitis is generally accepted as an autoimmune disease which is characterized by inflammation and cellular infiltration of the pituitary gland. It can be either primary or secondary. In this review, treatment of primary hypophysitis of various histological subtypes are discussed. Management of primary hypophysitis is usually symptomatic aiming to reduce the size of the pituitary mass and/or replace deficient pituitary hormones. Observation with replacement for deficient pituitary hormones can be applied in some group of patients. Keeping the complications of surgery in mind, surgical intervention should be limited to cases with severe and/or deteriorating compressive signs or cases with inconclusive findings of hypophysitis in whom treatment would be based on histopathological examination. The most commonly used drugs in the treatment of hypophysitis are glucocorticoids. They are able to reduce the size of the mass lesion with their anti-inflammatory effects and sometimes pituitary functions may also recover. However, there is no consensus about the optimal duration and dose of glucocorticoid use. When glucocorticoids and/or surgery fail, azathioprine, methotrexate, cyclosporin A and novel immunotherapies can be tried as third or forth line treatment. Radiotherapy and radiosurgery have been seldom used for treatment of hypophysitis in order to reduce the mass effect.