Thyrotropin-releasing hormone (TRH; protirelin) is the smallest known peptide hormone. It has central effects, unrelated to its endocrine effects, via an action at the pituitary-thyroid axis.TRH has been used successfully to treat children with neurological disorders including intractable epilepsy. The effectiveness of TRH, and an analogue of the peptide (DN-1417), has been reported as both add-on and monotherapy in the treatment of progressive myoclonic epilepsy. West syndrome, Lennox-Gastaut syndrome, complex partial seizures, severe myoclonic epilepsy in infancy, and early infantile epileptic encephalopathy. No serious adverse effects have been reported. TRH may, thus, be considered to be a possible treatment for intractable epilepsy, especially for children with West syndrome and Lennox-Gastaut syndrome. However, it should be noted that the studies were not placebo-controlled or double-blind in design, and most were performed in Japan (the peptide has not been widely studied as a treatment for epilepsy in other countries).The relatively prolonged duration of action of TRH may indicate that the mechanism of its anticonvulsant action differs from that of other anticonvulsant drugs. It is likely that TRH contributes to the plasticity of the seizure network, in analogy to its known trophic effect on spinal motoneurons. Additional research is required to further elucidate the mechanism of action of TRH in children who have epilepsy that is refractory to conventional treatment, and further efforts should be made to develop more potent and selective TRH analogues for neurological disorders.