Radioiodine therapy is used in the treatment of patients with differentiated thyroid cancer both to ablate residual thyroid tissue after initial surgery and to treat residual, recurrent, or metastatic cancer. In most institutions, therapy remains based on empirically determined, fixed amounts of radioiodine that do not account for individual differences in the mass of tissue to be treated and in radioiodine kinetics. Over the last 25 years, we have developed and refined techniques based on pre-therapy, diagnostic quantitative radiation dosimetry and imaging with 131I that permit individualized treatment which balances the success of the treatment and the risk of serious acute adverse effects on the bone marrow and lungs. In this manuscript we discuss patient selection and preparation for radioiodine therapy and outline in detail methods for performing quantitative dosimetry studies. Guidelines for the application of these results to the treatment of individual patients are presented.