Lissencephaly (LIS) is a neuronal migration disorder characterized by absent (agyria) or decreased (pachygyria) convolutions, producing a smooth cerebral surface. Subcortical band heterotopia (SBH) is a related disorder in which there are bilateral bands of gray matter interposed in the white matter, between the cortex and the lateral ventricles. This chapter discusses the genetic basis for diagnosis and pathogenesis of LIS. The LIS1 gene encodes a 45-kDa protein (PAFAH1B1), which functions as a regulatory subunit of platelet-activating factor acetylhydrolase (PAF-AH). It has been proposed that LIS1 colocalizes with microtubules and promotes their stabilization in vitro. The DCX gene encodes a 40-kDa microtubule-associated protein (DCX) which is expressed in migrating neuroblasts. X-linked lissencephaly with absent corpus callosum and ambiguous genitalia (XLAG) is a severe malformation syndrome that is only observed in boys. Lissencephaly with cerebellar hypoplasia (LCH) is associated with severe abnormalities of the cerebellum, hippocampus, and brainstem.