Exposure to maternal hypothyroxinemia during pregnancy, which is characterized by low free T4 but normal TSH levels, can negatively affect the fetus. This review provides an overview of present findings concerning the association between maternal hypothyroxinemia during pregnancy and childhood cognitive functioning. Possible causes of maternal hypothyroxinemia and potential mechanisms underlying this association are also discussed. Clinical and epidemiological studies suggest that maternal hypothyroxinemia in the first half of pregnancy but not later in pregnancy impairs cognitive development in infancy and childhood. Animal models confirm that the first half of pregnancy may constitute a sensitive period in which maternal hypothyroxinemia alters neurogenesis and causes neuronal migration errors in the developing fetal brain. However, observational studies in humans cannot demonstrate causality of the association between hypothyroxinemia and neurodevelopment. In the only completed randomized trial of antenatal thyroid screening and subsequent levothyroxine treatment of mild maternal subclinical thyroid dysfunction, including hypothyroxinemia, the interventions did not affect offspring IQ. More randomized trials are needed investigating whether screening for hypothyroxinemia and its treatment earlier in the first trimester of pregnancy can improve child cognitive functioning or prevent neurodevelopmental changes. Long-term observational studies should identify molecular, neuroanatomical, and neurophysiological factors involved in the association between maternal hypothyroxinemia and offspring cognitive functioning. Information on such mechanisms can be used for the development of innovative prevention and intervention studies that address maternal hypothyroxinemia and its potential consequences. This article is protected by copyright. All rights reserved.