Chronic pain has a high morbidity, complex etiologies and unclear mechanisms, which is a serious threat to human physiological and psychological health. The current analgesics exhibit poor effects on controlling chronic pain, with more adverse effects. Therefore, it is necessary to further elucidate the pathogenesis mechanism and explore novel, safe and effective therapeutic strategies for chronic pain. Recent studies have identified that caspase family is important in promoting nociception transmission in chronic pain, suggesting the possibility of targeting caspases for chronic pain management. This paper will review and summarize the underlying molecular mechanisms about the involvement of caspase family in chronic neuropathic pain (NP), inflammatory pain, cancer pain and musculoskeletal pain. New ideas will be provided for the treatment of chronic pain in clinical setting.