Cushing's syndrome constitutes a real challenge for the clinician who has to elucidate its etiology. ACTH determinations should allow to classify the etiology as belonging to either the ACTH-dependent or the ACTH-independent group, but variable biological characteristics of pituitary or ectopic ACTH secreting tumors may complicate the investigation. For small pituitary adenomas, magnetic resonance imaging (MRI) has increased the sensitivity of detection over CT scans; however, the small average size of 4-5 mm of corticotroph adenomas, including a significant proportion of tumors of less than 3 mm, limits MRI to a sensitivity which varies between 42-80%. In situations where a pituitary tumor is small (< 6 mm or not detectable by MRI), it is recommended to perform bilateral petrosal sinus sampling including a stimulation of ACTH secretion by CRH administration, to confirm the pituitary source of ACTH prior to undertaking pituitary exploration. Transsphenoidal selective removal of the pituitary corticotroph adenoma is the treatment of choice; immediate surgical success rate is high (75-90%) when the tumor is a microadenoma visible at MRI. However success rate decreases (50-60%) when surgical exploration is performed without radiological detection. The other end of the spectrum of size of the corticotroph adenomas includes either tumors larger than 10 mm (macroadenomas) or tumors invading the cavernous sinus; in either case, immediate success rate of surgical removal is only 50-70%. Radiotherapy coupled to medical (ketoconazole, op "DDD) or surgical (bilateral laparoscopic adrenalectomy) control of hypercorticism may be necessary. Longer follow-up series indicate a relapse rate of up to 25% after 10 years, suggesting frequent incomplete resection. It is hoped that further progress in our understanding of the molecular basis of the pathophysiology of this disease will allow the development of new therapeutic strategies which will circumvent the current limitations resulting in part, from the size of these tumors.