The 2013/59 EURATOM directive defines all nuclear medicine applications for therapeutic purpose as a form of radiotherapy and underlines the need of both justification and optimization of these procedures, including radioactive iodine therapy (RAIT) with [131I] for metastatic differentiated thyroid cancer (DTC). In metastatic DTC, optimal activity to be administered to achieve the best response rate with limited toxicity is still a matter of debate and international guidelines do not provide univocal recommendations on the preferable use of empiric versus a dosimetry-based approach in these patients. The purpose of this literature review is to describe the possible limits of dosimetry in RAIT planning according to methodological aspects, tumoral heterogeneity and to report clinical data on the impact on patients' outcome of different approaches. Due to the lack of standardized dosimetry protocols and clinical data assessing the superiority of a dosimetry-based vs an empiric approach in these patients, there is a need of standardisation and prospective, properly conducted studies to validate and to assess the best approach.