The diagnosis and differential diagnosis of Cushing's syndrome are challenging clinical problems in endocrinology. Traditional approaches have failed to provide adequate sensitivity, specificity, and accuracy for the diagnosis of Cushing's disease. During the past decade, new diagnostic tests and procedures have emerged and improved the ability to recognize even mild hypercortisolism and have provided the means to secure an accurate differential diagnosis. Despite these advances, new problems continue to surface and challenge clinical intuition. This article reviews new tests as well as new diagnostic problems in the evaluation of patients with suspected Cushing's disease.