Intra-vascular access is an unavoidable tool in sophisticated modern medical practice, and catheter-related infection remains a leading cause of nosocomial infections, particularly in intensive care units where it is associated with significant patient morbidity, mortality, and additional hospital costs. The incidence of catheter-related bloodstream infection ranges from 2 to 14 episodes per 1000 catheter-days. On average, microbiologically documented, device-related bloodstream infections complicate the use of a central venous line in three to five per 100 cases. But this represents only the visible part of the iceberg and most episodes of clinical sepsis are nowadays considered to be catheter-related. We briefly review the pathophysiology of these infections, highlighting the importance of the skin insertion site and the intravenous line hub as principal sources of colonization and infection. Principles of therapy are briefly addressed. A large proportion of these infections are preventable and this has been the objective of creating precise guidelines. It was recently suggested that the situation may evolve with the introduction of antibiotic/antiseptic-coated devices, whose impact on the epidemiology of antibiotic resistance remains to be determined. Recently, educational programs and/or a global preventive strategy based on the strict application of specific preventive measures and careful control of all factors associated with infection proved to be even more effective than coated devices in reducing rates of infection. Practical aspects regarding educational approaches will help clinicians to adapt and incorporate educational programs into clinical practice.