Cohort studies show that having a positive family history of stroke increases the odds of having a stroke by approximately 30%. The heritability of stroke appears to be heterogeneous across ischemic stroke subtypes, with cardioembolic stroke being least heritable. The relative influence of stroke risk attenuates with age, but genetics does not cease to be relevant in later adulthood. Recent family history and twin studies suggest that genetic factors remain relevant even beyond the seventh decade of life. One of the challenges of gene discovery in stroke relates to the complexities of phenotype. The complexities of phenotype can be addressed by focusing on individual ischemic stroke subtypes or by studying intermediate phenotypes like leukaraiosis, which has a heritability of approximately 70%. Although most stroke genetics research has focused on the identification of risk factor genes, an independent set of genes likely influences poststroke outcomes (for example, apolipoprotein E) and response to drug therapies (example, alpha-adducin and diuretic therapy).