Strokes occur in first-degree relatives of stroke patients at rates approximating 40%; estimated population prevalences range from 3%-12%. The recent discovery of the Strk1 gene in Icelandic families, associated with a 7-fold increased stroke risk in carriers, strongly implicates a genetic contribution to stroke independent of other genetically based risk factors such as hypertension or diabetes. In this article we review the evidence for genetic contributions to stroke. We describe roles for genetic and molecular epidemiology in evaluating this complex disease. We delineate study design issues and analytic strategies to determine genetic association.