Nelson's syndrome (NS) is an uncommon disease occurring as a complication of bilateral adrenalectomy (BLA) in patients with persistent Cushing's disease (CD) due to an adrenocorticotropin-producing pituitary tumor. The first reports of this syndrome were done in the 50s, although its pathophysiology is still not understood. Every year, between 1.8 and 2.6 cases are thought to occur per million people. It is characterized by hyperpigmentation, elevated adrenocorticotropic hormone (ACTH) plasma levels, and typical signs and symptoms related to pituitary adenomas, such as visual deficits due to optic pathway compression or decreased hormone production from the adenohypophysis. NS represents a challenge due to the lack of accepted diagnostic criteria and the complexity of its treatment. Moreover, the development of stereotactic radiosurgery (SRS) in the last few years has become an essential but controversial strategy for this syndrome. This review presents a comprehensive overview of NS.