In this review, we demonstrate how initial estimates of the risk of disease-specific mortality and recurrent/persistent disease should be used to guide initial treatment recommendations and early management decisions and to set appropriate patient expectations with regard to likely outcomes after initial therapy of thyroid cancer. The use of ongoing risk stratification to modify these initial risk estimates is also discussed. Novel response to therapy definitions are proposed that can be used for ongoing risk stratification in thyroid cancer patients treated with lobectomy or total thyroidectomy without radioactive iodine remnant ablation.