Central nervous system (CNS) malformations are among the more common forms of defects identifiable during fetal life. The wide availability of prenatal diagnostic ultrasound examinations has induced increasing awareness of genetic predispositions among obstetricians and their pregnant patients. Analogously, the greater sophistication of cytogenetic and molecular genetic techniques, and an increased willingness among geneticists to address complex traits, has resulted in strengthened interest among geneticists. The aim of this review was to provide an update on the state of the art in the field of genetic aspects of fetal brain malformations, paying special attention to single gene defects in either isolated or syndromic cases. We examined the role of genetics in neural tube defects, posterior fossa abnormalities, hydrocephalus, holoprosencephaly, corpus callosum agenesis and other, less frequent, CNS malformations. In some groups of malformation, molecular investigations have provided a useful insight into normal brain developmental pathways, and have also disclosed interesting information as regards pathogenetic mechanisms underlying non-genetic factors. Advances in neurology and genetics should enable easier, earlier and more accurate prenatal diagnosis to be mode and, in the near future, should contribute to the establishment of appropriate treatment and management for the fetus/eonate with CNS malformations.