Hypothyroidism is a clinical syndrome caused by thyroid hormone deficiency due to reduced production, deranged distribution, or lack of effects of thyroid hormone. The prevalence of hypothyroidism in developed countries is around 4–5%, whereas it is about 11% in India, only 2% in the UK, and 4·6% in the USA. It is more common in women than in men. Hypothyroidism has multiple etiologies and manifestations. The most common clinical manifestations are weight gain, loss of hair, cold intolerance, lethargy, constipation, dry skin, and change in voice. The signs and symptoms of hypothyroidism differ with age, gender, severity of condition, and some other factors. The diagnosis is based on clinical history, physical examination and serum level of FT3, FT4, and thyroid-stimulating hormone, imaging studies, procedures, and histological findings. The treatment of choice for hypothyroidism is levothyroxine, however; in this review article, we have discussed the epidemiology, etiology, clinical sign and symptoms, diagnosis, complications, and management of hypothyroidism in modern medicine and a comparative treatment by the Unani system of medicine (USM). In the USM, the main emphasis of the principle of treatment ( Usool-e-Ilaj ) is to correct the abnormal constitution ( Su-e-Mizaj ) and alter the six prerequisites for existence ( Asbab-e-Sitta Zarooriya ) to restore normal health. It is a packaged treatment, that is, different components of treatment are given as a package form which includes different drugs, dosages form, and regimens. Highlights – The concept of hypothyroidism has evolved over the centuries. It has been reported to be a woman-centric disorder. – There are several new subclasses of hypothyroidism based on the site of the lesion. – Levothyroxine has remained the treatment of choice. There has been little progress in managing the disorder. – The Unani system of medicine has been treating various manifestations of the disease since centuries with the help of crude drugs of herbal, animal, or mineral origin. – This review updates the concept and various dimensions of the disease hypothyroidism. – This review has enlisted new modalities for reducing the risk of hypothyroidism as stated in the literature of Unani medicine.