Some studies suggest that platelet activation and aggregation are associated with migraine, likely secondary to changes occurring during the acute attack. Evidence also suggests that platelet clots can lodge in small cerebral vessels, and that the resultant ischemia and inflammation can induce cortical spreading depression with aura-like symptoms and pulsatile headache. Endothelial dysfunction, a result of numerous vascular, genetic, and environmental risk factors, is more common in women with migraine and leads to altered hemostasis. When associated with other factors, such as oral contraceptive use, there may be an increased tendency for thrombus formation, secondary migraine with aura, transient ischemic attacks, and stroke. Identifying those migraineurs at highest risk of developing endothelial dysfunction and platelet disorders may allow for preventive strategies to avoid the cerebral consequences.