Infections associated with central venous catheters continue to be a major source of sepsis, particularly in hospitalized patients. In developing a strategy for the prevention of these infections, the source and route of invasion of the causative micro-organisms need to be considered. The main source of micro-organisms is the patient's skin. They can gain access to a catheter at the time of insertion, as well as via the external or internal catheter surfaces. Attempts to reduce the incidence of infections range from the type of skin preparation selected, to care of the insertion site post-catheterization. Improvements in catheter design have also reduced the likelihood of infection and include the development of non-leachable smooth catheters with anti-adhesive coatings. More recently, catheters containing antimicrobial agents have become available and preliminary studies have demonstrated a reduction in microbial colonization and associated sepsis. Future preventative strategies may include the application of low voltage electric current in combination with antimicrobials.