Radioiodine therapy (RIT) of thyroid functional autonomy (TFA) is rapidly evolving, though it has been recognized for decades as a very effective treatment of toxic nodular varieties. Indeed, TFA is a frequent cause of persistent subclinical hyperthyroidism, which should be regarded as a new metabolic syndrome, with well-established adverse cardio-vascular consequences. Sensitive TSH assays and multiparametric ultrasounds are not accurate enough to reliably diagnose TFA and identify its main variants, unifocal, multifocal (UFA/MFA) and disseminated autonomy (DISA). Modern diagnostic tools are extensively presented and rely upon Thyroid Scan imaging and quantification. A new relationship allows predicting at baseline, an excess of 123I uptake as compared to the TSH stimulation in compensated TFA. Suppressed TS are useful with either isotope, otherwise. Diagnosis of the DISA variant is presented as compared to Graves' disease. Dosimetry has some specificity in TFA work-up. Indeed, the spatial distribution of the dose is as important as the mean value itself and can be eventually controlled by adjusting the TSH level with the smart use of LT3 or antithyroid drug therapy (ATD). A review of the different ways to determine the target mass from anatomical to functional approaches is presented. Main clinical and dosimetric published results of RIT are summarized according to clinical goals. Endogenous TSH stimulation using an ATD preparation has promising results in reducing big autonomously functioning goiters. Finally, we report preliminary successful results of preventive RIT using short term LT3 suppression in compensated TFA, with low administered activities and low rate of hypothyroidism.