Significant events that have impacted healthcare over the last several years have been associated with escalating rates of healthcare-associated infections. This has resulted in increased efforts to reinstitute well-established and evidence-based infection prevention (IP) practices, particularly for central line-associated bloodstream infections. However, implementation of prevention initiatives beyond central lines has not received the same level of acknowledgment and response as being a considerable risk to patients. This article, authored by IP, infectious disease, and vascular access professionals, provides emerging perspectives and technical aspects associated with the complete "life cycle" of a vascular access device. The intent is to provide insight and perspective on enhancing current IP practices in the acute care hospital setting. This will also help prepare hospitals for upcoming broader surveillance and intervention activities aimed at reducing hospital-onset bacteremia and fungemia associated with all types of vascular access devices.