Nosocomial infections related to the development of catheter-related infections are a leading cause of morbidity and mortality among critically ill hospitalized patients. Despite important preventive efforts, these infections remains a daily concern for most clinicians. Significant improvements in the knowledge of their pathophysiology and diagnosis allow us to treat them more efficiently. Current practices such as guidewire exchange of catheters suspect to be the source of clinical sepsis are supported by indirect evidence only. Infected catheters should be systematically removed, but some of them may be salved by combining systemic and antibiotics-lock treatment. After reviewing some specific recent diagnostic and therapeutic aspects, we suggest a practical approach to manage catheter-related infections.