Background. Anaplastic thyroid cancer is a rare but aggressive disease with an extremely low survival rate. Improved diagnostic and therapeutic options have enabled the development of a multidisciplinary approach (surgery + radiation therapy + systemic antitumor therapy options) that has improved overall survival, highlighting the importance of a multidisciplinary approach. However, despite the widespread use of chemotherapy, targeted therapy and immunotherapy, patient outcomes remain disappointing. Objective. To analyze literature data on approaches to systemic therapy for anaplastic thyroid cancer, highlight the key disadvantages of existing treatment methods and identify promising areas of research in this area. Material and Methods. The literature search for the review was performed using the following databases: Web of Science, Scopus, MedLine, The Cochrane Library, and RSCI. During the literature search, 395 sources were analyzed, 59 scientific publications were selected. The review included studies covering the period from 1985 to 2024. Results. This review analyzes the current state of systemic therapy for anaplastic thyroid cancer. Chemotherapy remains one of the main methods of treatment, but its effectiveness is limited, and toxicity limits its use in weakened patients. Lack of sensitivity in patients with a target mutation and acquired resistance limit the effectiveness of targeted therapy, and insufficient efficiency and the need for waiting time for the effect to be realized limit the benefits of immunotherapy. Based on the results obtained, the most optimal treatment modality appears to be combination therapy (targeted therapy + immunotherapy). Conclusion. Despite advances in therapy modalities, prognosis for patients remains unfavorable. Further research is necessary to develop more effective and safe treatments. Particular attention should be paid to the study of the molecular mechanisms of the development of anaplastic thyroid cancer and resistance to systemic therapy, the search for new targets for targeted therapy and the improvement of approaches combined with immunotherapy.