I-131 therapy (RIT) in benign thyroid diseases is the oldest and most currently used application of internal radiotherapy. With the new molecular I-123-TS images one may identify 15 presentations that can benefit from RIT. With three groups of activity determination corresponding to a dozen approaching protocols, several judgmental criteria (eu-, hypo-, hyperthyroidism, relapses etc.) and varying timeframes to assess the success, a "best method of activity calculation" makes little sense. Four clinical objectives must be first identified (goal): antitoxic (euthyroidism), ablative (hypothyroidism), reductive (to reduce a targeted volume) and preventive (to prevent progression from compensated to overt hyperthyroidism) I-131-RIT. A dose response relationship as regards the target volume reduction is firmly established in the short term (1-year) and explains the clinical outcome in Thyroid Functional Autonomy (TFA). In Grave's disease (GD), other factors may interfere that make the long-term function less predictable. Pharmacological modulators of I-131-RIT such as antithyroid drugs (ATDs) and LT3 must be skillfully handled. ATDs interfere with iodine kinetics, enhance the heterogeneity of the spatial dose deposition and diminish the accuracy of absorbed dose deposition, especially when using poorly controlled dosimetric approaches. Short LT3 administration suppresses TSH that allows direct targeting of the autonomously functioning thyroid tissue. The three main groups and variants of activity calculation are presented in detail. Calculating the activity allows a 50% average reduction in the I-131 administered dose. Medical strategy should favour the informed patient's choice, after excluding the rare medical causes prompting discussion of an ablative approach. In TFA, low occurrence of hypothyroidism is the rule provided the treatment be given with a TSH < 0.1 mU/L, spontaneously or after LT3 suppression (compensated variety). In GD a long-term remission is rare (< 30%) and should be thoroughly discussed since it leads to euthyroidism in approximately 50% after a 12-year follow-up. Depending on the etiology (GD/TFA) and the 4 clinical goals, I-131 RIT planning is presented with optional choice of a patient adapted method of activity calculation and appropriate management of pharmacological modulators. (C) 2020 Published by Elsevier Masson SAS.