Since the introduction of sensitive assays for serum thyroid stimulating hormone (TSH) clinicians have advised hypothyroid patients to adjust the dose of levothyroxine (L-T4) in order to achieve a normal serum TSH. A minority of patients are dissatisfied with this treatment strategy and experience symptoms. Some indirect evidence suggests that a normal serum TSH may not necessarily reflect euthyroidism at tissue level in patients treated with L-T4. Increasingly hypothyroid patients demand higher doses of L-T4 or liothyronine (L-T3) or animal thyroid extract, often purchased online, and titrate the dose against symptoms, although ample evidence suggests that combination treatment (L-T4 with L-T3) is no more effective than L-T4 alone. Community surveys show that up to 53% of treated hypothyroid patients at any time have a serum TSH outside the normal range. The recommendation by guidelines that the upper limit of the normal range for serum TSH should not be exceeded is supported by robust evidence and is generally accepted by clinicians and patients. However, until recently the lower limit of serum TSH for optimal L-T4 replacement has been controversial. New evidence obtained by two independent large population studies over the past two years has shown that mortality of hypothyroid patients treated with levothyroxine is increased when the serum TSH exceeds or is reduced outside the normal reference range. It is estimated that implementation of a policy of normalising serum TSH in hypothyroid patients will reduce the risk of death of 28.3 million people in the USA and Europe alone.