Excess endogenous glucocorticoid production, whether ACTH dependent or ACTH independent, results in the classic clinical and biochemical picture of Cushing's syndrome. The diagnosis requires the demonstration of an increased cortisol secretion rate, best achieved by using the 24-hour UFC corrected for body surface area as an index. In mild cases, distinction from the hypercortisolism of pseudo-Cushing states may be difficult. A dexamethasone/o CRH test or close monitoring of the patient for a few months may be helpful. A discrete pituitary lesion on imaging and a standard oCRH test with results consistent with such a lesion are sufficient to proceed to trans-sphenoidal surgery. If no visible pituitary adenoma is present or if the oCRH test is equivocal, bilateral simultaneous inferior petrosal sinus sampling with oCRH administration is necessary to distinguish between a pituitary and an ectopic source. Surgical ablation is the treatment of choice for all types of Cushing's syndrome. In the 5% of cases with Cushing's disease in whom trans-sphenoidal surgery fails and in the 5% of cases in whom the disease recurs, repeat trans-sphenoidal surgery or radiation therapy in association with mitotane treatment may be pursued. Bilateral adrenalectomy effectively cures hypercortisolism if resection of the ACTH-secreting tumor is unsuccessful and radiation/medical therapy fails.