Leisure-time running is one of the most popular forms of physical activity around the world. It can be practiced almost everywhere and requires mainly a pair of “appropriate” running shoes. However, the term appropriate is ambiguous, and the properties of running footwear have always generated hot debates among clinicians, coaches, and athletes, whatever the level of practice. As the main interface between the runner's foot and the ground, the shoe potentially plays an important role in managing repetitive external mechanical loads applied to the musculoskeletal system and, thus, in injury prevention. Consequently, over the last decades, running shoes have been prescribed based on matching shoe features to foot morphology. This strategy aligns with the popular belief that footwear is one of the main extrinsic factors influencing running-related injury risk. Despite a seemingly sound strategy for shoe prescription and constant progress in running-footwear technology, the injury rate remains high. Therefore, our aim in this narrative literature review is to clarify whether the prescription of appropriate footwear to prevent injury in running is evidence based, the result of logical fallacy, or just a myth. The literature presented in this review is based on a nonsystematic search of the MEDLINE database and focuses on work investigating the effect of shoe features on injury risk in runners. In addition, key elements for a proper understanding of the literature on running footwear and injury risk are addressed. In this literature review, we outline (1) the main risk factors and the mechanisms underlying the occurrence of running-related injury, (2) important methodologic considerations for generating high-level evidence, (3) the evidence regarding the influence of running-shoe features on injury risk, (4) future directions for research, and (5) final general recommendations.