Lateral ankle sprains (LASs) are among the most common injuries incurred during participation in sport and physical activity, and it is estimated that up to 40% of individuals who experience a first-time LAS will develop chronic ankle instability (CAI). Chronic ankle instability is characterized by a patient's being more than 12 months removed from the initial LAS and exhibiting a propensity for recurrent ankle sprains, frequent episodes or perceptions of the ankle giving way, and persistent symptoms such as pain, swelling, limited motion, weakness, and diminished self-reported function. We present an updated model of CAI that aims to synthesize the current understanding of its causes and serves as a framework for the clinical assessment and rehabilitation of patients with LASs or CAI. Our goal was to describe how primary injury to the lateral ankle ligaments from an acute LAS may lead to a collection of interrelated pathomechanical, sensory-perceptual, and motor-behavioral impairments that influence a patient's clinical outcome. With an underpinning of the biopsychosocial model, the concepts of self-organization and perception-action cycles derived from dynamic systems theory and a patient-specific neurosignature, stemming from the Melzack neuromatrix of pain theory, are used to describe these interrelationships.