Levothyroxine sodium (LT4) is the treatment of choice for the management of hypothyroidism. The aim of the treatment is to obtain a permanent clinical and biological (normal TSH values) euthyroid state. Before initiating therapy, hypothyroidism has to be confirmed and, in adults, the risk of coronary heart disease to be evaluated. Adults require approximately 1.6-1.7 micrograms/kg/day for full replacement. Replacement doses may vary with various factors (age, weight, pregnancy, cause of the thyroid disease, degree of failure). Therapy is initiated gradually, usually starting with 50-100 micrograms LT4 in the adults without coronary heart disease risk. For older patients or patients at risk for cardiac disease, a lower initial dosage (12.5-25 micrograms LT4) and lower increments are indicated. Once the appropriate dose has been established, periodic monitoring, first at six months and then annually or every 6 months, is essential. Patients should not be evaluated before 6 weeks with the same dosage. Patient information is also important to improve compliance. Therapy for subclinical hypothyroidism is controversial. It is probably advisable if thyroid autoantibodies are positive and particularly if non specific signs or symptoms are present. Other forms (central hypothyroidism, iatrogenic transient and congenital forms, supra substitutive therapy for thyroid cancers) require a specific and specialised approach.