Current therapeutic options for patients with progressive thyroid cancer are relatively ineffective. There is a clear need to develop new alternatives for the management of this malignancy. As the knowledge of thyroid cancer biology advances, a large number of genetic events, molecular abnormalities, alterations of signaling pathways have been identified in the development and progression of thyroid neoplasms, and the potential exists to develop compounds targeted to treat thyroid cancers that do not respond to traditional therapy. In this review we described the recent development in thyroid carcinogenesis where the potential and novel intervention may exist. The discussion of thyroid carcinogenesis was integrated with exploitation of anti-thyroid agents that are currently either in clinical trials or in preclinical development for thyroid cancer.