Purpose <p>The American Thyroid Association (ATA) 2025 guidelines for the management of differentiated thyroid cancer (DTC) introduce significant updates for nuclear medicine physicians, focusing on a more individualized, patient-centered approach.</p> Methods <p>The purpose of this narrative review is to compare the 2025 and previous ATA guidelines for DTC, focusing on the implications for nuclear medicine.</p> Results <p>A major change is the revised risk stratification system, which now has four categories—low, low-intermediate, intermediate-high, and high—an advancement over the 2015 guidelines’ three-tiered system. This system is more comprehensive, integrating histopathologic features, imaging findings, and the patient’s response to therapy. It provides more detailed descriptions of factors like multifocality, vascular invasion, and includes new features like microscopically positive margins. Regarding radioiodine (RAI) therapy, the 2025 guidelines suggest an even more selective approach for low-risk patients to minimize side effects. For intermediate-risk patients, RAI seems to be indicated, despite the specific recommendation being quite open and potentially subjective of interpretation. The 2025 guidelines also prefer rhTSH over thyroid hormone withdrawal for patient preparation before RAI. The guidelines also give SPECT/CT a more prominent, routine role and expand the use of 18&#xa0;F-FDG PET/CT. Finally, the new guidelines provide a more detailed but still challenging definition of RAI-refractory disease, clarifying criteria for when further RAI treatment should be avoided.</p> Conclusions <p>The ATA 2025 guidelines represent a significant update for the management of DTC, with a significant impact on nuclear medicine efforts.</p>