Central venous catheters are commonly used in the critical care setting. Unfortunately, their use is often associated with complications, including fatal infections. Making the diagnosis of central venous catheter infection can be difficult. Additionally, resistance among the more common organisms that cause catheter-related infection is increasing. However, our understanding of the pathogenesis of catheter infection is improving through examination of biofilms. Also, our ability to diagnose catheter-related infections more accurately is improving with new techniques. There is new hope for ruling out catheter-related infection before removal by several methods, including a rapid enzyme-linked immunosorbent assay and the use of time differential for microbial growth between blood cultures obtained from a peripheral site and the catheter itself. Prevention through the use of barrier techniques and antimicrobial-coated catheters has been demonstrated to be of value in reducing catheter-related infection with these devices.