Differentiated thyroid cancer (DTC) is the most common thyroid cancer and is frequently encountered in clinical practice. The incidence of DTC has increased significantly over the past three decades. Surgical resection, radioactive iodine (RAI), and levothyroxine suppression therapy remain the primary modalities for DTC treatment. Active surveillance for low-risk thyroid cancer may be an alternative to immediate surgery for appropriately selected patients. Patient characteristics influence treatment selection and intensity. In the subset of patients with progressive distant metastatic disease, not amenable to treatment with surgery or RAI, novel agents, including targeted therapies and immunotherapy, should be considered.