Running after cycling is considered challenging for individuals performing triathlon and duathlon. An attempt to understand why athletes struggle to run after cycling has fostered interest from various studies. We collated data from many years of research (39 studies in total) in a systematic review exploring the biomechanical and physiological adaptations from the cycle-run transition. We observed that the perceived exertion is larger when running after cycling but no additional biomechanical or physiological parameter helped explain differences to a control run. In addition, interventions to improve the transition into running have shown conflicting outcomes. Coaches should explore individual responses from athletes in order to plan training activities as a way to improve running off the bike.