Despite the impact of high-visibility evidence-based clinical practice guidelines, physician adherence to guidelines remains low. This study explored primary care physicians' perceptions of barriers and facilitators in following the National Cholesterol Education Program guidelines. The authors conducted 9 focus groups and performed qualitative content analysis utilizing immersion-crystallization processes, codebooks, and qualitative coding software. Key barriers to implementing guidelines included the complexity and transience of existing cholesterol guidelines as well as perceived threats to multidimensional care of the patient that unifocal single-decision guidelines may create. Key facilitators included growing patient awareness regarding cholesterol, patients' willingness to take cholesterol medication, and technological breakthroughs. These findings have helped identify factors that prevent or enhance the adoption of cholesterol guidelines. While factors considered to be facilitators are significant, barriers may be sufficient to limit adherence. Opportunities may exist for improving adherence to cholesterol guidelines by providing training to providers and developing structural support through patient-physician activation tools.