Abstract: In recent years, targeted radionuclide therapy based on α-particles, namely targeted alpha therapy (TAT), has demonstrated unique advantages in the field of precision cancer treatment. Among various α-emitting radionuclides, ²¹¹At has become one of the radionuclides with the greatest potential for clinical translation owing to its physical characteristics, including a suitable half-life of 7.2 h, and the emission of a single α particle. The half-life of ²¹¹At is highly compatible with the processes of radiopharmaceutical preparation, quality control, and clinical administration, thereby facilitating radiopharmaceutical preparation and clinical application. The authors systematically reviewed the physical, chemical, and radiobiological characteristics of ²¹¹At, outlined its radiolabeling methods, summarized the latest clinical trial progress of ²¹¹At-based TAT in ovarian cancer, thyroid cancer, hematological malignancies, prostate cancer, and other malignant tumors, provided an outlook on its development in precision cancer therapy, and discussed the challenges encountered in clinical practice, which aimed to provide a reference for the research and clinical translation of ²¹¹At-based TAT.