Adenosine is an inhibitory modulator of brain activity with neuroprotective and anticonvulsant properties. Adenosine levels are regulated mainly by adenosine kinase (ADK), an enzyme that is responsible for the removal of adenosine via phosphorylation to AMP. Recent evidence indicates that expression of ADK undergoes rapid coordinated changes during brain development and following brain injury, such as after epileptic seizures and stroke. Thus, transient downregulation of ADK after acute brain injury protects the brain from seizures and cell death. Conversely, chronic overexpression of ADK causes seizures in epilepsy and promotes cell death in epilepsy and stroke. These findings have direct implications for the rational definition of ADK as a therapeutic target. In recent years, novel treatment strategies have been developed that make use of the intracerebral transplantation of cells that are ADK deficient and, thus, release adenosine. A new era of cell-based delivery of adenosine has begun, which holds great promise for novel therapies for epilepsy and stroke.