Anatomy and physiology courses are a foundation for numerous degrees, but experience some of the highest failure rates of all undergraduate health science programs (Higgins-Opitz & Tufts, 2014). While interventions have been developed in an attempt to remediate this concerning phenomenon, there is a paucity of evidence to determine the reason anatomy and physiology courses pose such an obstacle to students, and whether there are reliable early determinants for student success in these courses. This review will discuss why this obstacle exists, and the factors that contribute to success and failure in undergraduate anatomy and physiology courses.