Thionamide-derived antithyroid drugs (ATD) have been in use for over half a century and much is now known about their mechanism of action, pharmacokinetics and clinical pharmacology. Candidates for first option ATD therapy are young adults, without large goitre. The recommended initial dose for patients without big goitre and mild hyperthyroidism is 20 mg of MMI/CBZ. The recommended maintenance doses are 5-10 mg of MMI/CBZ. In cases of big goitre and/or severe hyperthyroidism the recommended initial dose is 30 to 40 mg/day. PTU use should be restricted to first trimester of pregnancy, doses should be as low as possible (150 to 200 mg/day) and then changing to MMI is recommended. Treatment Duration should be of 12-18 months. ATD plus thyroxine combination therapy have not advantage on ATD alone. ATD plus L-Thyroxine regimens should be used to avoid hypothyroidism when patients are with maintenance doses of ATD drugs in order to relax monitoring. In this case a low dose of T4 50-75 µg per day is used. Breast feeding women with hyperthyroidism can be treated with MMI/CBZ. ATD will not stop until serum stimulating TSH-receptors antibodies values are within the normal range. We are waiting for results of ongoing studies of biochemical and/or genetic markers that will permit us to predict the outcome of these patients after ATD treatment is stopped.