The usual first treatment for Cushing’s disease is surgical removal of the pituitary adenoma. In patients in whom surgery is unsuccessful or who decline an operation, radiation to the pituitary offers the possibility of remission. No form of radiation delivery results in immediate control of cortisol production. Thus, until radiation treatment becomes effective, medical therapy to lower cortisol production is indicated. The time to remission with radiation therapy cannot be predicted, medical therapy should be discontinued every 6 months to assess response to radiation treatment; a normal 24 h urine free cortisol being the optimal outcome. There are no prospective studies comparing the results among the different types of radiation delivery. The type of radiation delivery depends on several factors, including the availability of different treatment modalities and the size of the target area (focused high dose radiation with the Gamma knife is not suitable for a large lesion close to the optic nerves or optic chiasm). All types of radiation delivery cause loss of normal pituitary function and patients should be monitored regularly (every 6 months) for development of new hypopituitarism and appropriate hormone replacement(s). Complications of radiation therapy may include adverse effects on vision, normal brain tissue, and with older methods of fractionated radiation delivery, vasculopathy with an increased risk of cerebrovascular disease. Current use of more targeted methods of delivery will hopefully reduce this risk. If pituitary surgery is unsuccessful and the patient undergoes bilateral adrenalectomy, without pituitary radiation, there is a substantial risk, approximately 50% of patients, of development of Nelson’s syndrome (growth of pituitary adenoma, increase in serum ACTH, hyperpigmentation). There is a role for pituitary radiation in the treatment of patients with Cushing’s disease, most commonly as adjunctive therapy after unsuccessful pituitary surgery. Regular medical monitoring is necessary to determine the effectiveness of radiation therapy and development of new pituitary hormone deficiency.