The administration of radioactive iodine-131 (131I) is one of the representative traditional targeted therapy for post-surgical differentiated thyroid carcinoma (DTC). As DTC tumor cells largely preserve the capability of thyroid follicular epithelial cells, including the expression of the sodium iodide symporter (NIS), 131I can be selectively internalized by these cells once introduced into the body. The simultaneous emitting of both γ-ray and β-ray from 131I featured its unique theranostic value in managing DTC, through γ-ray to detect the residual thyroid tissue and DTC lesions via nuclear medical imaging, while through β-ray to yield the precise tumoricidal effect as well as remnant thyroid ablation. This theranostic potential of 131I significantly enhances progression-free survival, disease-specific survival, and overall survival in DTC patients with residual/recurrent/metastatic lesions as long as they are capable of iodine uptake. Nevertheless, the clinical application of 131I, despite its “precise” treatment philosophy, remains far from precision medicine while clinical practice, which urges further refinement in pre-treatment assessment, dosage tailoring, and post-treatment efficacy evaluation to fully capitalize on its theranostic benefits. Recently, with the accumulation of evidence-based medical data, 131I treatment has evolved with respect to treatment principles, pre-treatment risk stratification, post-treatment dynamic assessment, and comprehensive patient management, with an aim to optimize the diagnostic and therapeutic precision of 131I. Here we briefly review and update the recent advance on 131I management on DTC.