Sports medicine physicians and physiotherapists commonly use cryotherapy (eg, ice application) postinjury to decrease tissue temperature with the objective of reducing pain, limiting secondary injury and inflammation, and supporting healing. However, besides the analgesic effect of cryotherapy, a literature search revealed no evidence from human studies that cryotherapy limits secondary injury or has positive effects on tissue regeneration. Thus, our current understanding of the potential mechanisms and applications of cryotherapy largely relies on the results from animal studies. Importantly, treatment should not aim at obliterating the inflammatory and regeneration processes but instead aim to restore an adapted/normal regulation of these processes to improve function and recovery. However, some animal studies suggest that cryotherapy may delay or impair tissue regeneration. With the translation of laboratory animal studies to human sport medicine being limited by different injury and muscle characteristics, the effect of cryotherapy in patients with musculoskeletal injuries is uncertain. Thus, pending the results of human studies, cryotherapy may be recommended in the first 6 hours following an injury to reduce pain (and possibly haematoma), but it should be used with caution beyond 12 hours postinjury as animal studies suggest it may interfere with tissue healing and regeneration.