Ankle sprains are among the most common injuries sustained by athletes and seen by sports medicine physicians. Despite their prevalence in society, ankle sprains still remain a difficult diagnostic and therapeutic challenge in the athlete, as well as in society in general. The purpose of this section of our two-part study is to review scope of the problem, the anatomy and biomechanics of the lateral ankle ligaments, review the pathoanatomical correlates of lateral ankle sprains, the histopathogenesis of ligament healing, and define the mechanisms of injury to understand the basis of our diagnostic approach to the patient with this common acute and chronic injury. We extensively review the diagnostic evaluation including historical information and physical examination, as well as options for supplementary radiographic examination. We further discuss the differential diagnosis of the patient with recurrent instability symptoms. This will also serve as the foundation for part two of our study, which is to understand the rationale for our treatment approach for this common problem.