The correct diagnosis and an appropriate classification of hypothyroidism must be considered on the light of the most recent physiopathological and molecular information. Hypothyroidism is no longer regarded as the rare disease characterized by a myxedematous condition as described since one century ago. With the present improvement of the diagnostic tools the thyroid hypofunction now includes all those blunted forms that are classified as subclinical or latent hypothyroidism. Thus, the hypothyroid syndrome, previously considered a rare event in its overt form, reaches a prevalence of 14% in female aged over fifty years. Following a coherent, concise historical review, the influence of age, surgery, drugs and autoimmunity on the etiology of the disease are critically discussed. The early detection and treatment of congenital hypothyroidism, to avoid an irreversible damage of the central nervous system, by means of the screening on the paper spot is also stressed. Replacement therapy with synthetic levothyroxine has to be personalized, according to the age and other clinical conditions, and should be prescribed also in the treatment of subclinical hypothyroidism.