The administration of antiplatelet therapy is paramount in the management of the patients with coronary artery disease, especially undergoing percutaneous coronary intervention (PCI) to reduce the rate of thrombotic events. Nowadays, oral double antiplatelet therapy with the use of low-dose aspirin plus one P2Y12 inhibitor is the cornerstone. The oral antiplatelet agents have some potential drawbacks such as insufficient platelet inhibition in the first hours after acute coronary syndrome or the dependence on enteric absorption. Nevertheless, the only intravenous agents commercially available are aspirin, the P2Y12 inhibitor cangrelor, and the two glycoprotein IIb/IIIa receptor inhibitors (GPIs), eptifibatide and tirofiban. The development of the GPIs was focused on reaching faster platelet inhibition and reduced the risk of thrombotic complications associated with PCI and/or acute coronary syndrome (ACS). Nevertheless, several clinical trials showed the benefits of I.V. administration in ACS patients but counterbalanced by increased risk of bleeding complications in their routinely use. Therefore, GPI role is, nowadays, marginal and represents an option for reducing thrombus burden in bail-out situations. Cangrelor is a reversible antagonist of the platelet P2Y12 receptor. It does not require any bioactivation, therapeutic plasma concentrations are immediately achieved, and its plasma half-life is short. The rapid onset/offset pharmacological profile makes it potentially suitable for different applications such as P2Y12 receptor inhibitor-naïve patients undergoing PCI, bridge to surgery therapy or patients with cardiogenic shock and comatose survivors of out-of-hospital cardiac arrest undergoing PCI. In this chapter we discuss the current evidence and clinical applications of this class of antiplatelet drugs and their potential role to address some drawbacks of oral agents.