Optimal treatment of patients during percutaneous coronary interventions (PCIs) is constantly changing as clinical trials provide new and clinically relevant information. Clinicians need to be aware of this information to incorporate these new strategies into clinical practice, leading to improvements in the care of patients. The direct thrombin inhibitor, bivalirudin, will play an increasingly important role as the primary anticoagulant for PCIs because it meets the criteria as a safer, cost-effective, and convenient agent in a spectrum of clinical scenarios. This article will provide practical guidelines to assist the interventional cardiologist to prepare his or her patient for PCI and will focus on some of the more common and more difficult patient cohorts, in particular those patients with chronic kidney disease as well as the elderly, 2 of the fastest growing groups of patients undergoing PCI.