Hypoxia is a major stress to the fetal development and may result in irreversible injury in the developing brain, increased risk of central nervous system (CNS) malformations in the neonatal brain and long-term neurological complications in offspring. Current evidence indicates that epigenetic mechanisms may contribute to the development of hypoxic/ischemic-sensitive phenotype in the developing brain in response to fetal stress. However, the causative cellular and molecular mechanisms remain elusive. In the present review, we summarize the recent findings of epigenetic mechanisms in the development of the brain and their roles in fetal hypoxia-induced brain developmental malformations. Specifically, we focus on DNA methylation and active demethylation, histone modifications and microRNAs in the regulation of neuronal and vascular developmental plasticity, which may play a role in fetal stress-induced epigenetic programming of hypoxic/ischemic-sensitive phenotype in the developing brain.