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The ketogenic diet (KD) is increasingly being used to treat patients with intractable epilepsy. Despite decades of research, the reason for its success, when anticonvulsants have failed, is still not completely understood. There are, however, many candidate mechanisms which can be grouped into those that alter neuronal excitability at the synapse, and those that confer neuroprotection. The molecular underpinning of these mechanisms centres on the shift from glucose- to lipid-based energy generation that accompanies a high fat/low carbohydrate diet.