Over the years a number of high quality studies has established the effectiveness of external measures (tape, brace) and neuromuscular training for the prevention of ankle sprains. The general conclusion derived from these studies is that recurrent ankle sprains can be effectively prevented using any of these measures, and that measures are cost-beneficial. Nevertheless, despite the commonness of this type of injury and the availability of effective measures, implementation of prevention in clinical practice is lagging behind. In addition, although proven effective, a link between biomechanical and neurophysiological adaptations as a function of preventive measures, leading to clinical and functional improvements and ultimately ankle sprain recurrence prevention, has never been fully made. The current evidence on ankle sprains and their prevention provides ample opportunities to pursue a translational approach through which fundamental knowledge will provide guidance to specify the effective preventive program to its bare essentials and decrease user-burden while retaining full effectiveness.