The goal of vascular access devices is to provide for the administration of the therapies required to help the patient recover while causing the least amount of damage to the patient's vascular system. One of the ways to preserve patient vasculature is through the prevention of infections associated with these devices. The central line bundle, created by Peter Pronovost in a landmark study known as the keystone study in Michigan, consists of five components that, when strictly adhered to during the insertion of a central line catheter, are known to reduce the risk of catheter-related BSIs. The five components include hand hygiene, maximal barrier precautions during insertion, use of chlorhexidine as a skin antisepsis, optimal catheter site selection with avoidance of the femoral vein for central venous access in adult patients, and daily review of line necessity with prompt removal of unnecessary lines. These five components to prevent infection during the insertion of a central catheter are reviewed within this chapter. Care and maintenance considerations, equally important in the prevention of infection, are covered in detail throughout the rest of this book.