Cerebrovascular accidents (strokes) are a challenge to modern health care throughout the world because they contribute greatly to morbidity, disability, and mortality rates. Ischemic stroke constitutes the majority of cases of cerebrovascular accidents. It is a complex multifactorial polygenic disease, i.e., it develops under the influence of conventional risk factors and the genetic component. The latter is formed by the joint contribution of many independent or interacting polymorphic genes. Current studies of the genetic susceptibility to ischemic stroke use two approaches based on the analysis of the association between polymorphic sites of the genome and the disease, including the candidate-gene approach and genome-wide association studies, followed by a meta-analysis of the results. This review considers the published data on genetic susceptibility to ischemic stroke, which may be a starting point for the investigation of molecular mechanisms that determine the pathophysiology of ischemic stroke. Although some progress has been made in this field, the problem of identifying genetic risk factors that could be used as markers for predicting individual susceptibility to ischemic stroke is still far from a complete solution. The main obstacle to this is the low replication of the results. It can be overcome by investigating ethnically uniform populations and clinically distinct IS forms.