Nuclear magnetic resonance (NMR) spectroscopy permits noninvasive, serial measurements of several metabolites with important neurobiologic roles in localized brain regions in vivo. Over the last decade, this technique has been applied to investigations of both animals and humans with epilepsy. Several nuclei that include specific proton, phosphorus, and carbon isotopes provide NMR signals that measure specific compounds in vivo. This paper reviews the studies that have used these multinuclear NMR techniques to investigate the role of these methods in the diagnosis and pathogenesis of epilepsy.