The administration of heparins (unfractionated or fractionated) represents the current standard as anticoagulant treatment during percutaneous coronary intervention in different clinical settings (elective cases and acute coronary syndrome). Since the incidence of heparin-induced thrombocytopenia (HIT) is expected to range between 0.1 and 5%, the application of an appropriate anticoagulant agent has become a mandatory issue. This review will provide current pathophysiological insights of HIT as well as contemporary alternative anticoagulant strategies during PCI in patients with or at risk of HIT.