Abstract: Pain is a protective response in physiological states, which protects the body from further harm and facilitates species survival. However, in pathological states, pain becomes a common disease/symptom significantly affecting the quality of life in patients. Recent years have seen great progress in understanding of pain mechanisms and the development of anesthetic agents, but a number of questions and challenges still remain. The current article is aimed to systematically summarize the historical experience in this field and look forward to the future, in order to push the studies concerning pain mechanisms and the development of anesthetic agents to a much higher level.