Ketogenic diets are high in fat and low in carbohydrates and represent a well-established and effective treatmentalternative to anti-epileptic drugs. Ketogenic diets are used for the management of a variety of difficult-to-treat or intractableseizure disorders, especially pediatric refractory epilepsy. However, it has been shown that this dietary therapycan reduce seizures in people of all ages, and ketogenic diets are being applied to other prevalent medical conditions suchas diabetes. Although used effectively to treat epilepsy for nearly 90 years, the mechanism(s) by which ketogenic dietswork to reduce seizures remain ill-understood. One mechanism receiving increased attention is based on findings that ketogenicdiets increase the brain energy molecule ATP, and may also increase the levels and actions of the related endogenousinhibitory neuromodulator adenosine. ATP and adenosine have both been identified as important modulators of seizures;seizures increase the actions of these purines, these purines regulate epileptic activity in brain, adenosine receptorantagonists are pro-convulsant, and adenosinergic mechanisms have been implicated previously in the actions of approvedanti-epileptic therapeutics. Here we will review recent literature and describe findings that shed light on mechanistic relationshipsbetween ketogenic diets and the purines ATP and adenosine. These emerging mechanisms hold great promisefor the effective therapeutic management of epileptic seizures and other neurological conditions.