Objective: The aim of this systematic review was to summarize evidence on the acute responses of individuals with Prader-Willi syndrome (PWS) to physical exercise, and on the effectiveness of long-term exercise interventions to improve the clinical manifestations of this syndrome. Design/methods: Relevant articles were identified in the electronic databases PubMed, Medline, CINAHL and SPORTDiscus (from inception to December 2018). Twenty-two studies including a total of 356 patients with PWS met all inclusion criteria and were included in the review. Results: Patients with PWS present with a decreased physical performance and impaired cardiorespiratory (maximal oxygen consumption, heart rate recovery after exercise) and hormonal (growth hormone release) responses to exercise. Most long-term exercise interventions have proven to decrease body mass while improving physical performance. Some benefits have also been reported in biochemical (glucose homeostasis, lipid profile) and biomechanical (gait pattern) variables, although there is controversy regarding the effects on body composition. No exercise-related adverse events have been reported in patients with PWS. Conclusion: Physical exercise seems to be safe and effective for improving several phenotypes in PWS, notably physical fitness. However, further research is needed to confirm these results and especially to corroborate whether exercise per se or combined with dietary intervention is an effective coadjuvant treatment for reducing body mass in these patients.