SummaryThe need for therapy for nodular goiter results from the growth of thyroid nodules over decades and from the possibility of tracheal compression and worsening of respiratory function. Given the high prevalence of non-toxic goiter, the epidemiologically low incidence of clinically apparent thyroid cancer justifies non-surgical strategies. Randomised studies have shown that levothyroxine offers limited therapeutic effects and is inferior to radioiodine therapy regarding goiter shrinkage. When indication for a definitive therapy is given, the choice between resection and radioiodine therapy should consider volume of goiter, severity of clinical symptoms, thyroid uptake, patient’s age, co-morbidity, previous resection of goiter, patient’s profession and patient’s wish. Even in large goiters between 100 and 300 ml radioiodine therapy showed consistent results with goiter size reduction from 35-40% one year and 40-60% two years after radioiodine therapy. Thyroid hormones to prevent recurrence of goiter are not necessary. Recurrent goiters were seldom observed after radioiodine therapy and resulted from initially very large goiters or uptake in dominante nodules or from low 131I activities. Recombinant human TSH (rhTSH) offers the opportunity to enhance the effect of radioiodine therapy. Observational studies have shown that rhTSH increases low 131I uptake in case of high alimentary iodine-supply by the factor 4, causes a more homogenous 131I distribution within the goiter and improves goiter reduction. A phase I study for dose finding is running in the USA. Conclusion: Radioiodine therapy for shrinkage of large non-toxic goiter should not be restricted to elderly patients, or to patients with co-morbidity or high operative risk, but is an attractive alternative to surgery in patients with special professions (singer, teacher, speaker) or with the wish for a non-invasive treatment modality.