The increased survival of very low birth weight (VLBW) premature infants has been associated with an increased prevalence of transient disorders of thyroid function during the early weeks of life. All VLBW infants have relatively low, and gestation age-dependent, thyroxine-binding globulin (TBG) concentrations associated with variably low total thyroxine (T4) concentrations. These infants also have a high prevalence (30%-60%) of nonthyroidal illnesses that impact thyroid function, including total and free iodothyronine concentrations. Finally, thyroid gland hormone biosynthesis and the hypothalamic-pituitary axis are relatively immature and thyroid glandular iodine stores are low. As a result, VLBW infants manifest a high prevalence of transient primary hypothyroidism (0.41%) and transient hypothalamic-pituitary (thyrotropin [TSH] deficiency) hypothyroidism (5%-10%?). Thyroid function should be monitored in VLBW infants during the first 1-4 weeks of life to detect these disorders as well as the much less common permanent congenital hypothyroidism. An elevated serum TSH level (> 20 mU/L) is diagnostic of primary hypothyroidism and a low free T4 concentration with a normal or low serum TSH level suggests hypothalamic-pituitary hypothyroidism. Treatment of transient or permanent primary hypothyroidism and of congenital TSH deficiency is indicated. Preliminary data suggests that 30-60-day treatment of transient hypothalamic-pituitary hypothyroidism improves IQ at 2 years of age. However, further information confirming the benefit of treatment, the threshold free T4 values for diagnosis, and the optimal dose of T4 are necessary.