Brain ischemia occurs when the blood flow to the entire brain (global) or part of the brain (focal) is interrupted. In the clinic, brain ischemia is most often a consequence of cardiac arrest or ischemic stroke, 2 common medical emergencies that constitute a leading cause of death or long-term disability worldwide. Sadly, current treatment options for brain ischemia are extremely limited. Thus, there is an urgent need to identify novel cerebroprotective interventions that will improve quality of life for survivors. This can only be achieved through detailed dissection of various aspects of the pathophysiology of brain ischemia in the experimental setting. To this end, basic brain ischemia research needs to leverage highly reproducible animal models and modern technologies. Moreover, previous translational failures in the field have taught us that pre-clinical models of cardiac arrest or stroke should recapitulate relevant patient characteristics, eg, comorbidities and advanced age. In particular, age has a defining influence on how the brain responds not only to an ischemic insult, but also to therapeutic interventions, and most cardiac arrest and stroke patients are elderly. Therefore, inclusion of aged animals in experimental brain ischemia research has been increasingly endorsed. The goal of this Methods Collection is to demonstrate novel experimental models of ischemic stroke and cardiac arrest that can be applied in aged animals, and to exhibit cutting-edge technologies that enable sophisticated analyses in experimental brain ischemia research.