Clinical practice guidelines are an important result of evidence-based research. However, current clinical practice remains out of step with the rapid pace of research advancements. Often, decades pass before research is translated into clinical practice. The National Comprehensive Cancer Network (NCCN) has created evidence-based clinical guidelines to promote effective clinical practice. Formerly, the NCCN established guidelines to reduce cancer-related infections only for neutropenic patients; however, they have expanded their guidelines beyond neutropenia to prevent and treat cancer-related infections. Implementing scientific evidence into clinical practice is challenging and complex, and healthcare professionals should understand barriers to implementing clinical practice guidelines to ensure successful translation into practice. This article provides a brief review of NCCN guidelines and describes common barriers encountered during implementation. In addition, a conceptual framework is offered to help identify and address potential concerns before and after adoption of guidelines.