The goals of this narrative review are to provide a brief overview of the muscle and tendon adaptations to eccentric resistance exercise and address the applications of this form of training to aid rehabilitative interventions and enhance sports performance. This work is centered on the author contributions to the Special Issue entitled "Eccentric Exercise: Adaptations and Applications for Health and Performance". The major themes from the contributing authors include the need to place greater attention on eccentric exercise mode selection based on training goals and individual fitness level, optimal approaches to implementing eccentric resistance exercise for therapeutic purposes, factors that affect the use of eccentric exercise across the lifespan, and general recommendations to integrate eccentric exercise in athletic training regimens. The authors propose that movement velocity and the absorption or recovery of kinetic energy are critical components of eccentric exercise programming. Regarding the therapeutic use of eccentric resistance training, patient-level factors regarding condition severity, fitness level, and stage of rehabilitation should govern the plan of care. In athletic populations, use of eccentric exercise may improve movement competency and promote improved safety and performance of sport-specific tasks. Eccentric resistance training is a viable option for youth, young adults, and older adults when the exercise prescription appropriately addresses program goals, exercise tolerability, and compliance. Despite the benefits of eccentric exercise, several key questions remain unanswered regarding its application underscoring the need for further investigation.