Management and therapy of conditions of the thyroid, parathyroid glands, and cervical lymph nodes have evolved rapidly during the past 15 years. The development and continued improvement of high-resolution ultrasound (US) equipment, US-guided biopsy, and image-guided ablative techniques have fueled this change. These technical improvements and the knowledge and experience gained during this time have decreased the rate of unnecessary surgery in patients with thyroid nodules. They have also allowed more limited neck dissection in patients with parathyroid adenomas and have led to the development of US-guided ablative techniques that have eliminated the need for surgery in some cases. This article reviews the rationale and techniques of US-guided biopsy of the thyroid, parathyroid, and cervical lymph nodes. Established and evolving ablative techniques of these structures are also examined.