In this issue of Blood, Zhu and colleagues clearly demonstrate that advanced glycation end products (AGE), generated under hyperglycemic conditions, can specifically interact with CD36 on platelets. This interaction can trigger CD36-dependent JNK2 activation, enhance platelet aggregation, and accelerate thrombus formation. Thus, AGE-CD36–mediated platelet hyperreactivity may play an important role in the increased risk of arterial thrombosis in diabetic patients.