Ischemic stroke is a heterogeneous multifactorial disorder recognized by the sudden onset of neurologic signs related directly to the sites of injury in the brain where the morbid process occurs. The evaluation of complex neurologic disorders, such as stroke, in which multiple genetic and epigenetic factors interact with environmental risk factors to increase the risk has been revolutionized by the genome-wide association studies (GWAS) approach. This article reviews salient aspects of ischemic stroke emphasizing the impact of neuroepidemiology and GWAS.