In many instances, the pathophysiology of thyroid dysgenesis (TD) remains as yet unclear and until relatively recently the disorder was usually regarded as occurring in a sporadic manner. However, over the past few years, a small but significant proportion of familial cases has been identified (2%) through the study of subjects with congenital hypothyroidism and more recent work has revealed an even higher proportion of familial TD in both symptomatic or asymptomatic individuals (7.9%). Together, these studies strongly point to a significant genetic component of this disorder. Moreover, detailed observations of members affected by different types of TD in the same family suggest that TD could be an entity with a common underlying mechanism for all the etiological groups. To date, molecular genetic studies have implicated four genes in thyroid development and some mutations have been reported in affected subjects. Three of these encode transcription factors while the forth encodes the thyrotropin hormone receptor. However, their involvement in the general TD population remains questionable, as only a few mutations have been reported so far and as linkage analysis has demonstrated the relevance of other genes. Therefore, further work is required to fully understand the pathophysiology of TD.