In patients with thyroid nodules, ultrasound (US) imaging represents an indispensable tool for assessment of the risk of malignancy. Over approximately four decades, innovative technology and successive improvements have facilitated its entry into the routine management and greatly improved its predictive value. When US features cannot reliably rule out thyroid cancer, US guidance allows a correct and safe sampling also of small or deeply located thyroid lesions. Obtained in this way, cytological or microhistological specimens may reliably define the nature of most thyroid nodules, and the information from histochemical or molecular markers shows promise in the classification of the remaining indeterminate cases. While a prompt surgical treatment can be offered in the minority of suspicious or definitely malignant cases, most individuals warrant only a follow-up. However, at initial evaluation, or over the years, a fraction of these benign lesions may grow and/or become symptomatic. Such cases may benefit from US-guided minimally invasive procedures as an alternative to surgery. Image-guided percutaneous treatments most often achieve relief of neck complaints, are inexpensive, and can be performed on an outpatient basis. The risk of major complications, after adequate training, is very low. Importantly, thyroid function is preserved. Currently, percutaneous ethanol injection for cystic lesions and thermal ablation, with laser or radiofrequency, for solid nodules are increasingly used and disseminated beyond the initial core facilities. In centres with expertise and high patient volume, their use should be considered as first-line treatment alternatives to surgery for selected patients with benign enlarging or symptomatic thyroid lesions.