Subclinical hypothyroidism can be diagnosed in 1% to 10% of the adult population, is more common in women, and increases with age. In many patients, treatment with L-thyroxine reduces low-density lipoprotein cholesterol, improves cardiac function, reduces symptoms of hypothyroidism, and diminishes neuropsychiatric symptoms. Treatment also reduces the likelihood of statin-induced myopathy. However, in double-blind, placebo-controlled trials of L-thyroxine therapy in subclinical hypothyroidism, cardiovascular and symptomatic benefits have been neither uniform nor definitive. In the absence of a large-scale, multicenter, randomized trial, physicians have to individualize therapy for each patient. Benefits of therapy are most likely to be realized in patients with thyroid-stimulating hormone levels greater than 10 mU/L on repeated measures, those with hypothyroid symptoms, those who are pregnant, those with a documented family history of hypothyroidism, and those with severe hyperlipidemia.