Headaches are common complaints in children. The International Classification of Headache Disorders, 3 edition (beta version), defines more than 280 types of headaches. Primary headaches refer to independent conditions that cause pain and include migraine, tension-type headaches (TTH), and trigeminal autonomic cephalalgias (TACs). Several agents are involved in the pathogenesis of headaches. The factors associated with predisposition to atherosclerosis seem to be particularly important from the clinical point of view. The influence of obesity on the incidence of headaches has been well established. Moreover, idiopathic headaches, especially migraine, are thought to be one of the first signs of disorders in lipid metabolism and atherosclerosis. The risk of migraine increases with increasing obesity in children. Another factor that seems to be involved in both obesity and headaches is the adiponectin level. Recent data also suggest new potential risk factors for atherosclerosis and platelet aggregation such as brain-derived neurotrophic factor (BDNF), sCD40L (soluble CD40 ligand), serpin E1/PAI I (endothelial plasminogen activator inhibitor), and vascular endothelial growth factor (VEGF). However, their role is controversial because the results of clinical studies are often inconsistent. This review presents the current knowledge on the potential markers of atherosclerosis and platelet aggregation, which may be associated with primary headaches.