P2Y12 is a Gi-coupled 7TM receptor belonging to the P2Y family of nucleotide receptors. The principle ligand for P2Y12 in vivo is ADP, although it binds with lesser affinity to ATP. P2Y12 is expressed predominantly in platelets, where it mediates ADP-induced stable aggregation and secretion. The antithrombotic drugs clopidogrel and ticlopidine disrupt P2Y12-mediated platelet aggregation, and are indicated in acute coronary syndromes. However, metabolites of each drug that are generated by hepatic cytochrome P450 activity are the actual entities that bind and antagonize P2Y12 directly. Novel P2Y12 antagonists that bind directly to P2Y12 exhibit a faster onset of action, and are undergoing clinical trials.