Anaplastic thyroid carcinoma (ATC) is a rare type of malignancy of thyroid follicular cell origin. It is one of the most aggressive human cancers, and typically associated with a fatal prognosis. Most patients are presenting as locally advanced and systemically disseminated disease. A single mode of therapy, whether it is surgery, chemotherapy, or radiotherapy, fails to afford significantly favorable outcomes. While multimodality approaches may enhance the treatment response to a small degree, such implementations of these modalities are often impractical as many patients are of old age and are unable to tolerate the intensity of treatments. As in many other types of carcinomas, radical resection may be the mainstay of therapy for ATC, but surgery itself is seldom possible for this condition. Even with aggressive surgical therapy for those invasive ATCs, there is no evidence of decreased recurrence rates, while only the post-surgical morbidity rates increase. One chemotherapeutic agent that seems to demonstrate some effect against ATC is adriamycin, which is more effective when administered in combination, and is also known to act synergistically with radiotherapy. A commonly employed treatment modality is the combination therapy of adriamycin and cisplatin administration with hyperfractionated radiation therapy. Other chemotherapeutic agents proven to be effective are taxanes such as paclitaxel and docetaxel. Despite of disappointing result of conventional radiotherapy, however, hyperfractionated radiation therapy and combined chemotherapy has been suggested to improve survival rates by some institutions, while others disagree. The dismal results of conventional treatments for ATCs have stimulated the investigation for new therapeutic methods with improved outcome. There have been a number of trials of new materials or therapeutic methods. In recent studies, some trials were partially successful or promising in vitro or in vivo. The examples of these trials are; redifferentiation therapies, molecular targeted therapies, and some other miscellaneous methods. Although the observations may suggest that some of the methods may have a therapeutic effect on ATCs, or may act as an adjunct to other primary treatment modality, the efficacy and safety have not been ascertained yet in human trials, and further confirmation through in-depth studies are required.