In this review, we discuss the latest results concerning the molecular analysis of antibodies (Ab) directed toward thyroid autoantigens. In particular, we attempt to define patterns within the Ab repertoire that correlate best to their activities. Whilst a considerable amount is now known concerning the Ab response to thyroid peroxidase (TPO), there is still much we do not understand. We review evidence for the site of interaction of TPO-reactive Ab with native TPO. The Ab responses to thyroglobulin (Tg) and, in particular, the thyroid-stimulating hormone receptor (TSH-R), are much less well characterised. In this review, we focus on the molecular analysis of the Ab response to Tg and TPO, assessing the repertoire as it is currently known. In addition, we have tried to link this information with the analysis of the epitopes recognised by the various Ab. Finally, we discuss one of the more unusual features of the thyroid Ab repertoire, the use of D-D fusion at heavy chain junctions, and questions raised by our current state of knowledge, such as the role of Ab using germline V regions in antigen recognition.