Unfractionated heparin (UFH) as well as low-molecular-weight heparins (LMWH), especially enoxaparin, are recommended by the current international guidelines for routine used in the conservative treatment of patients with acute coronary syndromes (ACS). UFH is still the recommended antithrombin as soon as percutaneous coronary interventions (PCI) are performed, although the results of different trials clearly have demonstrated the benefit of enoxaparin also in interventional cardiology. Bleeding complications along PCI procedures can be minimized by avoiding crossover from enoxaparin to UFH or vice versa and by reducing the dosage of indirect antithrombins, particularly of enoxaparin, in patients with chronic renal dysfunction and/or the elderly. Especially for those patient groups, bivalirudin offers already today an effective alternative. There is increasing expectation concerning the use of bivalirudin in patients undergoing PCI procedures but firm data exist at present only for low- and medium-risk patients with non ST-elevation ACS. Results of still ongoing trials (ACUITY, HORIZONS) will help to further confirm the role of bivalirudin in patients with high-risk acute coronary syndromes. For other direct antithrombins, e.g., fondaparinux (a pentasaccharide) or melagatran, comparably few data are available at present. Whether these agents will make their way into clinical use, future will tell.