Giant-cell arteritis (GCA) is the most common vasculitis affecting large vessels in the elderly. It is associated with ischemic events that account for important disability. Despite the increasing insight in the mechanisms involved in the arterial wall inflammation, the events that lead to eventual occlusion of the vessels lumen are unknown. Cohort studies on risk factors for ischemic events and aspirin efficiency in GCA provide inconsistent results. Corticosteroids, which prevent the worsening or the recurrence of ischemia in the majority of patients, are slow-acting and not effective in all patients. The interaction between circulating activated platelets and leukocytes contributes in acute myocardial infarction and other ischemic diseases to determine the prothrombotic and inflammatory characteristics of blood cells. The activation of circulating platelets, their interaction with leukocytes and the expression of tissue factor by circulating leukocytes frequently occur in patients with GCA. The molecular characterization of the cross-talk between blood cells and the inflamed vessel wall could yield molecular targets for novel therapeutics, more effective than aspirin in preventing ischemic events and more specific than steroids in their treatment.