Papillary (PTC) and follicular (FTC) thyroid cancer (TC) belong to differentiated thyroid cancer (DTC). The initial treatment of DTC is surgery followed by radioiodine remnant ablation. Although the prognosis of DTC is generally good, approximately 10-15% of DTC patients will devolp advanced disease and their disease will become radioiodine refractory. Even in radioiodine refractory patients the natural history of disease can be slowly progressive or indolent.The expanded knowledge of the the biological basis of DTC has opened new opportunities in therapy – targeted therapy, aimed at inhibiting specific molecular targets and pathways in tumor proliferation, survival and progression. We rewieved different tageted therapies in DTC. Sorafenib was the first and only targeted drug approved by FDA for progressive and radiodine-refractory DTC. Also, lenvatinib had promising efficacy results in phase III trial, probably even better than sorafenib, but with more treatment-related deaths. The timing of targeted therapy for DTC is of decisive importance. The potential benefit should be balanced with potential toxicity of targeted therapies.