Neuroimaging has greatly assisted the diagnosis and treatment of epilepsy. Volumetric analysis, diffusion-weighted imaging, and other magnetic resonance imaging (MRI) modalities provide a clear picture of altered anatomical structures in both focal and nonfocal disease. More recently, advances in novel imaging methodologies have provided unique insights into this disease. Two examples include manganese-enhanced MRI (MEMRI) and diffusion tensor imaging (DTI). MEMRI involves injection of MnCl(2) to evaluate neuronal activity where it is actively transported. Areas of neuronal hyperactivity are expected to have altered uptake and transport. Mapping of activation along preferential uptake pathways can be confirmed by T(1)-weighted imaging. DTI uses the intrinsic preferential mobility of water movement along axonal pathways to map anatomical regions. DTI has been used to investigate white matter disease and is now being applied to clinical and, to a lesser extent, animal investigations of seizure disorders. These two diverse MRI methods can be applied to animal models to provide important information about the functional status of anatomical regions that may be altered by epilepsy.