Barefoot running has become a popular research topic, driven by the increasing prescription of barefoot running as a means of reducing injury risk. Proponents of barefoot running cite evolutionary theories that long-distance running ability was crucial for human survival, and proof of the benefits of natural running. Subsequently, runners have been advised to run barefoot as a treatment mode for injuries, strength and conditioning. The body of literature examining the mechanical, structural, clinical and performance implications of barefoot running is still in its infancy. Recent research has found significant differences associated with barefoot running relative to shod running, and these differences have been associated with factors that are thought to contribute to injury and performance. Crucially, long-term prospective studies have yet to be conducted and the link between barefoot running and injury or performance remains tenuous and speculative. The injury prevention potential of barefoot running is further complicated by the complexity of injury aetiology, with no single factor having been identified as causative for the most common running injuries. The aim of the present review was to critically evaluate the theory and evidence for barefoot running, drawing on both collected evidence as well as literature that have been used to argue in favour of barefoot running. We describe the factors driving the prescription of barefoot running, examine which of these factors may have merit, what the collected evidence suggests about the suitability of barefoot running for its purported uses and describe the necessary future research to confirm or refute the barefoot running hypotheses.