The cloning and sequencing of thyroid-stimulating hormone (TSH) receptor (TSHR), combined with advances in molecular techniques, have facilitated the understanding of the interaction of the TSHR antibodies (TSHRAbs) with the TSHR at the molecular level and have allowed the delineation of their clinical role. TSHRAbs in vivo are functionally heterogeneous; the stimulating TSHRAbs cause hyperthyroidism and diffuse goiter in patients with Graves' disease, whereas, the blocking TSHRAbs cause hypothyroidism in some patients with autoimmune hypothyroidism and are the cause of transient neonatal hypothyroidism. Measuring TSHRAbs has potential clinical implications in differential diagnosis of Graves' disease, predicting the outcome of Graves' disease after antithyroid drug treatment, and predicting the fetal/neonatal hyperthyroidism or neonatal hypothyroidism. The existence of epitope heterogeneity in a patient, i.e., of stimulating TSHRAbs with epitopes other than on the N-terminal region of the extracellular domain, is significantly associated with favorable long-term clinical response to antithyroid drug treatment. Measuring these subtypes for thyroid-stimulating antibody (TSAb) has potential clinical impli-cations, for example, in predicting responsiveness to treatment in untreated patients with Graves' disease.