In this presentation, David A Mankoff, MD, PhD, examines a variety of interrelated topics-the use of iodine dosimetry to calculate a maximum tolerated dose for I-131 in metastatic thyroid cancer and patients with altered iodine clearance; the avoidance of bone and hematological toxicity; I-131 therapy using recombinant TSH stimulation versus thyroid hormone; and the ways and means to define iodine refractory disease in patients with progressing thyroid cancer.