Recent findings demonstrated that the two isoforms of the Na+/Ca2+ exchanger, NCX1 and NCX3, which are involved in several pathophysiological aspects of cerebral ischemia, can be included among the members of the growing family of the mediators involved in the ischemic brain tolerance due to their ability to regulate neuronal calcium homeostasis (Figure 1). The gene discussed is SLC8A3; the disease is brain ischemia.