This comprehensive review examines the evolving role of radioiodine (RAI) therapy in differentiated thyroid cancer (DTC) management amidst ongoing controversies. While RAI remains integral for high-risk and metastatic DTC, its benefit in low- and intermediate-risk groups is increasingly questioned. Evidence from randomized trials suggests that low-dose RAI (≤30 mCi) is as effective as higher doses for remnant ablation, with minimal added risks. In low-risk patients, recent studies indicate limited survival benefit, favoring active surveillance and personalized approaches. For intermediate-risk cases, RAI’s impact on recurrence and survival remains conflicting, emphasizing the need for tailored treatment decisions. The review also discusses RAI-related risks, including secondary primary malignancies, and the significance of optimal dosing, personalized dosimetry, and RAI-refractory definitions. Recent advances in imaging and molecular profiling promise more precise, risk-adapted strategies in the management of well-differentiated DTCs. Ultimately, high-quality prospective trials are essential to refine guidelines, improve outcomes, and minimize unnecessary exposure in DTC management.