The sport of open water swimming (OWS) has been popularized on a global scale. This population of athletes may experience several unique medical conditions, necessitating a review of medical issues and environmental considerations. Clinicians providing care for OWS athletes should be educated and trained to recognize and manage illnesses and conditions that often occur in an effort to ensure athlete safety. This article focuses on the major medical challenges faced in OWS, including a review of cardiorespiratory conditions and infections, competitor factors, water quality concerns, and risk minimization strategies.