Stroke is a leading cause of morbidity and mortality in most developed countries. Despite the enormous social and economic toll that it extracts, there remains no effective therapy for stroke. A very small group of patients have been treated with some benefit with thrombolytics; however, the short therapeutic time window and the potential for life-threatening side effects limit the effectiveness of this approach. Therefore, with the ultimate aim of developing better therapies, a considerable research effort over the past decade was mounted in the quest to better understand the pathophysiology of brain ischemia. The deprivation of oxygen and nutrients in cerebral ischemia initiates a cascade of complex biochemical and neurophysiological alterations in the brain. Consequently, and being the most sensitive brain cells, neurons are injured and die first, followed by glia and endothelial cells. Cerebral ischemia also triggers an inflammatory reaction in the brain with influx of leukocytes and the production of a host of mediators including cytokines, matrix metalloproteinases, and reactive oxygen species. One group of molecules that could have a central role in this context are the chemokines.