Anaplastic thyroid cancer is one of the most lethal malignancies, with dismal prognosis, resistance to multimodal treatments and a median survival of only 5-6 months. Advances in the discovery of genetic pathway aberrations involved in this aggressive disease have been made, and multiple novel therapies targeting these pathways are undergoing clinical trials. So far, there is no single effective treatment for this disease; however, multimodal therapies with a combination of surgery, radiation and chemotherapy hold some promise. We conducted a PubMed search using the words thyroid neoplasm, anaplastic thyroid carcinoma, anaplastic thyroid cancer and anaplastic thyroid neoplasm, revealing 1673 publications. We review the pathophysiology, current treatments and advances made in identifying the alterations in genetic pathways, as well as novel therapies targeting these pathways.