The importance of the optimization of the up front management of DTC cannot be underestimated. An aggressive approach is advocated, except in situations widely accepted to be low risk (i.e., female patients <40 y, with tumors <1.0 cm confined to the gland). Distant tumor greatly reduces the chances for survival in all patients. The loss of iodine-concentrating ability removes systemic radioiodine from the therapeutic equation and thereby virtually eliminates chances for cure. The role of chemotherapy in non iodine responsive DTC is still in question, and a benefit in advanced disease has not been established. For non iodine-concentrating tumor that cannot be approached surgically, external beam therapy remains an option, both within the neck and for dominant foci of distant metastatic tumor (i.e., brain and bone). Any distant lesion demonstrating the capacity for radioiodine uptake also should be addressed with (131)1, because this will potentially treat tumor not evident on diagnostic survey. In conclusion, (131)1 has demonstrated efficacy for the postsurgical management of DTC. Although its acute and long-term side-effect profile is not especially worrisome relative to other forms of systemic cancer therapy, the administration of (131)1 is not entirely without risk. Taking into account many of the issues described in this article, the administration of (131)I should in every case be optimized. It also should be applied carefully and judiciously to patients expected to derive benefit.