Hashimoto’s thyroiditis, also known as chronic lymphocytic thyroiditis and struma lymphomatosa, is a chronic autoimmune disease characterized by painless, diffuse enlargement of the thyroid gland occurring predominantly in middle-aged women. The patients are often euthyroid, but hypothyroidism may develop. The thyroid parenchyma is diffusely replaced by a lymphocytic infiltrate and fibrotic reaction. Patients with Hashimoto’s thyroiditis have serum antibodies reacting with thyroglobulin (Tg), thyroid peroxidase (TPO), and against an unidentified protein present in colloid. The increasing use of needle biopsy and serologic tests for antibodies has led to much more frequent recognition of Hashimoto’s thyroiditis, and there is reason to believe that it may be increasing in frequency. A patient with a small goiter and euthyroidism does not require therapy unless the TSH level is elevated. The presence of a large gland, progressive growth of the goiter, or hypothyroidism indicates the need for replacement thyroid hormone. Surgery is rarely indicated. Development of lymphoma, though very unusual, must be considered if there is growth or pain in the involved gland. With early diagnosis, proper levo-thyroxin (L-T4) replacement therapy, regular patient follow-up care, and attention to early detection and management of complications, the prognosis in Hashimoto’s thyroiditis is excellent, with patients leading a normal life. This chapter addresses a wide range of topics related to Hashimoto’s disease, including epidemiology, pathology, etiology, pathogenesis, clinical manifestations, diagnosis and differential diagnosis, association with papillary thyroid carcinoma, management, and prognosis.