Ischaemic stroke is the most common form of stroke and is caused by atherosclerosis in most patients. Several genetic determinants contribute to stroke risk. Of these, carotid intimal-medial wall thickness (IMT) is particularly relevant, because it is a surrogate measure of subclinical atherosclerosis and a strong predictor of future ischaemic stroke. Studies of twins, siblings, and families have provided significant evidence for heritability, but the genes involved have not been identified. Some researchers have reported that IMT is high in people with functional variants of genes related to matrix deposition (MMP3), inflammation (interleukin 6), and lipid metabolism (hepatic lipase, APOE, CETP, and PON1). In this review, we assess the robustness of these associations and examine whether there is any evidence of risk modification by factors, such as smoking.