Transient hypothyroxinemia of prematurity (THOP) is a typical entity of the preterm infant, affecting the majority of preterm infants, born less than 30 weeks of gestational age. It is defined as a temporary postnatal reduction from cord values in serum levels of T4 and FT4, but with normal thyroid-stimulating hormone (TSH) levels.The etiology of THOP is complex and multifactorial. Loss of maternal T4, limited postnatal thermogenesis, hypothalamic-pituitary immaturity, limited thyroid gland reserve, persistent fetal thyroid hormone metabolism and predisposition to nonthyroidal illness syndrome are several factors that contribute in less or more intensity to THOP.The association between THOP and poor neurodevelopmental outcome is well established and several therapeutic clinical trials have been set up. However, there is currently no evidence for prophylactic or therapeutic supplementation with thyroxine (T4) for premature infants with THOP. One study of van Wassenaer et al. showed a beneficial effect of treatment of THOP in a subgroup of preterm infants with gestational age less than 28 weeks, but a reverse effect in the group with a gestational age of 29 weeks. This is an illustration of the limited comprehension of the pathophysiology of THOP.