Epilepsy, a common disease affecting 1% to 2% of the population, is characterized by seizures, hyperexcitability at synapses, and aberrant extension of neurons following seizures. Much work has been done on the role of synaptic components in the pathogenesis of epilepsy, but relatively little attention has been given to the potential role of the cytoskeleton. The neuronal cytoskeleton consists of microtubules, actin filaments, intermediate filaments, and associated proteins. A number of mutations in both microtubule-associated proteins (MAPs) and actin-binding proteins, as well as altered expression levels of several cytoskeletal proteins, are known to be involved in epilepsy. These changes will affect the dynamics of the neuronal cytoskeleton and therefore are likely to contribute to the pathogenesis of epilepsy through mechanisms such as increased neurotrophic support to neurons and increased sprouting of mossy fibers. These changes may also contribute to hyperexcitability of neurons through an as yet unidentified mechanism.