Pituitary enlargement and hyperpigmentation following bilateral adrenalectomy for Cushing’s disease is termed as Nelson’s syndrome. The cause of pituitary enlargement is the loss of feedback by the adrenal glucocorticoids following bilateral adrenalectomy. The tumor in Nelson’s syndrome is aggressive and is treated by surgery and/or pituitary radiation. Following bilateral adrenalectomy, prophylactic pituitary radiation sometimes prevents the development of Nelson’s syndrome; however, this leads to an increased risk for hypopituitarism. Previously, bilateral adrenalectomy was the preferred treatment for Cushing’s disease; however, with the advent of better localization and improved techniques of transsphenoidal surgery, primary pituitary surgery is now the preferred treatment for Cushing’s disease.