The diagnosis of endogenous Cushing syndrome (CS) remains challenging and generally unfolds in two steps: first, the definitive determination of the presence of CS and second, the determination of the underlying cause. New definitive diagnostic tests, including late-night salivary cortisol, combination low-dose dexamethasone suppression testing (DST) and salivary cortisol testing, and combination CRH-DST testing appear promising. Traditional diagnostic tests, including urine-free cortisol and low-dose DST, remain important in the definitive evaluation for CS. Lowering of the serum cortisol cutoff value for low-dose DST will improve sensitivity but likely adversely impact specificity. Recent studies suggest that subtle hypercortisolism may be found in patients with adrenal incidentalomas, diabetes, hypertension, or obesity without specific physical manifestations of CS, suggesting a subclinical form of the syndrome. It remains to be determined which population, if any, should be screened for CS. In determining the etiology of CS, a plasma ACTH level will help differentiate between ACTH-independent and ACTH-dependent CS. Central venous sampling should be considered in patients with equivocal standard test results to help differentiate between CS and ectopic ACTH syndrome. In centers with limited expertise in central venous sampling, internal jugular vein sampling with CRH stimulation may be the preferred invasive test given its relative simplicity.