In modern interventional cardiology, the central circulation is accessed for many reasons, ranging from coronary imaging and intervention, to hemodynamic measurement, myocardial biopsy, valvular interventional procedures, diagnosis and treatment of congenital heart disease, and multiple other indications. Each of these indications requires a careful assessment of potential sites for vascular access. Each access point may have distinct advantages and disadvantages. For example, radial arterial access or brachial venous access may be particularly appropriate in some patients with coagulopathy due to a lower incidence of bleeding. Femoral venous access on the right is often the preferred approach for patients needing a trans-septal approach to the left side of the heart. Thus each procedure requires careful consideration of both patient-specific and procedural factors can vary widely. Technical factors play an important role as does the coagulation system. Some patients have inherent abnormalities of hemostasis (such as hemophilia) while others may have acquired bleeding risk (such as thrombocytopenia in hepatic failure). Some patients will have cultural issues that interact with the treatment of bleeding such as in Jehovah’s Witness patients. A rapidly expanding array of anticoagulation medications used to treat thrombotic disorders add complexity to interventional procedures.