Over the past decade, several advances have been made in our understanding of the molecular pathogenesis of pituitary adenomas, and novel diagnostic tests for the diagnosis and differential diagnosis of Cushing's syndrome have been developed. Although established in the late 1970s, measurement of UFC has emerged as the most sensitive and specific test to screen for and confirm the presence of Cushing's syndrome. The combined CRH/DST is potentially a useful adjunct in patients with probable pseudo-Cushing's syndrome and borderline elevated urinary cortisol levels. Improved assays for circulating ACTH levels are now used as the first test in differentiating ACTH-dependent from ACTH-independent sources. HDDST with the revised reference ranges for UFC currently remains the primary test for differentiating pituitary from ectopic ACTH secretion. However, the CRH test may replace the HDDST in the foreseeable future because of its lower rate of false-positive and false-negative results. IPSS has been established as an integral part of the evaluation of patients with suspected Cushing's disease and no conclusive (> 0.8 to 1 cm) pituitary adenoma. Advances in the radiolabeling of small peptides, such as somatostatin analogs, may facilitate the search for occult ectopic sources.