Serum thyroglobulin measurement has greatly facilitated the clinical management of patients with differentiated thyroid cancer and a variety of other thyroid disorders. Thyroglobulin autoantibodies remain a significant obstacle to the clinical use of thyroglobulin measurement. The interpretation of any given thyroglobulin value requires the careful synthesis of all pertinent clinical and laboratory data available to the clinician. The diagnostic use of rhTSH-stimulated thyroglobulin levels has greatly facilitated the follow-up of low-risk patients with thyroid cancer. Although the measurement of thyroglobulin mRNA from peripheral blood is likely to affect the future management of these patients, it is expected that serum thyroglobulin measurement will continue to have a principal role in the care of patients with differentiated thyroid cancer.