Clinical and experimental interest in the ketogenic diet has grown rapidly over the past decade. Ketone bodies have been linked to inhibitory neurotransmitter release and activation of ATP-sensitive potassium channels. The ketogenic diet enhances overall cellular bioenergetics and reduces oxidative stress. Glycolytic diversion and/or restriction may play an important role in the clinical activity of the ketogenic diet. Modulation of tricarboxylic acid cycle flux may also underlie ketogenic diet effects.