The ketogenic diet (KD) produces ketone bodies which have been believed to have anti-seizure effects. Experimental evidence shows that ketone bodies can have various anti-seizure properties including activation of inhibitory adenosine and ATP-sensitive potassium channels, enhancement of mitochondrial function, reduction in oxidative stress, and attenuation of excitatory neurotransmission. Although there are pragmatic challenges in administering ketone bodies in humans, the use of ketone esters or balanced ketone electrolyte formulations may largely mitigate prior concerns and induce sustained hyperketonemia to achieve therapeutic effects.