Epilepsy is a neurological disorder characterized by a long-lasting predisposition to recurrently generate unprovoked seizures. Epilepsy affected over 70 million people worldwide, with approximately one third suffering from pharmacoreisitant seizures. Currently, the clinic antiseizure drugs have not the efficacy in alteration of epilepto-genesis. Adenosine, as an endogenous anticonvulsant, inhibits the development of ep-ilepsy via interaction with the molecular epileptogenic network on several levels: i) Activation of A1 receptor inhibits glutamate release via presynaptic inhibition, and hyperpolarize the synaptic potentials in post-synaptic neurons. ii) A2A receptor on as-trocyte interacts with glutamate transporter GLT-1, controlling glial glutamate homeo-stasis. iii) Activation of A3 receptor inhibits GABA transporter type 1 -mediated GABA uptake. iv) Adenosine kinase (ADK) is highlighted as a pathological hallmark of epi-lepsy. The short isoform adenosine kinase (ADK-S) in the cytoplasm of astrocytes, controls the extracellular levels of adenosine and hence adenosine receptor-mediated mechanisms. The long isoform of adenosine kinase (ADK-L) in the nucleus of astrocytes and a subset of neurons, modulates adenosine receptor independent epigenetic mech-anisms. In the present review, we focus on some of the most recent and exciting pro-gresses including mechanisms, evaluation biomarkers for epilepsy as well as therapy aim to modify the progression of epilepsy.