Adults with diabetes are 2-4 times more likely to suffer from heart disease or ischemic stroke than adults without diabetes, yet standard antiplatelet therapy, which is the cornerstone for primary and secondary prevention of cardiovascular disease, fails in many patients with diabetes. Three independent but often interrelated variables that contribute to platelet hyperreactivity-high blood glucose, oxidative stress, and elevated vascular shear forces-coexist in patients with diabetes, creating a perilous concurrence of risk factors for cardiovascular events. Recent research has focused attention on the plateletspecific collagen receptor glycoprotein VI (GPVI) as a potential antithrombotic target. Signaling events downstream of GPVI are influenced by hyperglycemia, oxidative stress, and shear stress. Importantly, drugs targeting these GPVI signaling pathways are already in existence. The potential to repurpose existing drugs is a high-gain strategy for yielding new antiplatelet agents and could have particular benefit in individuals with diabetes.