PURPOSE: Nelson's syndrome is a severe complication of bilateral adrenalectomy performed in the treatment of some Cushing's diseases, and its management remains difficult. Trough the observation of a patient suffering from a severe form of Nelson's syndrome for more than 10 years, the authors review the literature and discuss the main current therapeutic possibilities. CURRENT KNOWLEDGE AND KEY POINTS: Many molecules have been used with variable results. In our observation cabergoline at 2 mg per week seems to be efficient after a 3 and a half years follow-up, in accordance with some recent publications. More than bromocriptine, this dopamine agonist provides interesting prospects for this disease's management. Moreover, if the conventional treatments as valproic acid or cyproheptadine are not very efficient, somatostatin analogs seem to be of some therapeutic interest. FUTURE PROSPECTS AND PROJECTS: New molecules are currently evaluated, but studies are difficult to conduct because of the low disease prevalence. Tumour receptors analysis undoubtedly constitutes an attractive way to find new therapeutic targets.