The current review aims to investigate the barriers to and facilitators of the adherence to clinical practice guidelines (CPGs) in the Middle East and North Africa (MENA) region. English language studies published between January 2010 and May 2019 were searched on PubMed, Embase, and EBSCO. The barriers were categorized as clinician-related factors, such as lack of awareness of familiarity with the CPGs, and external factors, such as patients, guidelines, and environmental factors. The search identified 295 titles, out of which 15 were included. Environmental factors, specifically lack of time, resources, incentives, availability, and costs of treatment or diagnostic tests, training, and dissemination plans were the most commonly identified barriers. The familiarity with or awareness of healthcare professionals about the guideline, guideline characteristics, lack of agreement with the guidelines and preference in clinical judgment, physician self-efficacy, and motivation were reported to a lesser extent. Few studies reported on the compliance of facilitators with the guidelines including disseminating and advertising guideline materials, education and training on the guidelines, regulatory and financial incentives, and support from institutions. The review highlights that the studies on barriers to and facilitators of compliance with CPGs in the MENA region are limited in number and quality.