Chronic ankle instability (CAI) is common, disabling, and represents a significant socioeconomic burden. Current treatment options are not adequately efficacious. CAI is multifaceted, yet it is commonly addressed in terms of either mechanical instability or functional impairment. Both are inherently linked. Basic research must be conducted to foster reliable translational research encompassing both mechanical and functional aspects. A review was conducted to identify CAI risk factors for inclusion in future studies, and we offer here opinions and perspectives for future research.