Central venous access devices are a major source of nosocomial infection. The skin and catheter hub are the two major sources for the introduction of the colonizing organisms. Authors reviewed up-to-date prophylactic possibilities in this paper. Prophylactic measures include a skilled team, topical disinfectants, topical antibiotics, new types of devices such as coating catheter with antiseptic agent and catheter with silver impregnated cuffs, maximal barrier precautions during insertion, systemic vancomycin therapy of high risk patients. Exchanging central venous catheters over a guidewire might be useful diagnostically but have not been used to be of any therapeutic or prophylactic goal. Prophylactic antibiotic lock of device and use of fibrinolytic agent to clean the device may be useful but can not be a standard recommendation.