Through its actions on regulatory genes that form, grow and sculpt the brain, thyroid hormone (TH) is essential for human brain development. Although much of what we know about these effects is based on research with rodents, recent studies of children exposed to TH insufficiencies during critical stages of early development provide preliminary evidence on how and when the human brain needs TH. This paper reviews some of the major studies from both the rodent research and research on offspring of women with hypothyroidism during pregnancy and children with congenital hypothyroidism (CH) who were assessed using neuropsychological tests and with advanced neuroimaging techniques. The final section will compare findings from children lacking TH due to maternal hypothyroidism and CH conditions, whose loss of TH at different times represents unique time windows for examining TH effects in the human brain.