 This study examined the barriers and facilitators to implementing clinical practice guidelines for rare diseases. The authors identified key barriers and facilitators at both the individual health professional and guideline levels. At the individual health professional level, the most commonly reported barrier was lack of familiarity with the recommendation, followed by lack of domain knowledge and difficulty in implementing the guideline. At the guideline level, the most commonly reported barrier was resource constraints such as technology costs, ancillary staff costs and more cost-effective alternatives. Additionally, there was a paucity of studies reporting influential people, patient advocacy groups or organizational factors influencing implementation. This article was authored by Matthew Gitters, Jihan Chong and Thea Sutton, and others.