Background　Opioids are the cornerstone therapy for the treatment of moderate to severe pain. However， they are often associated with side effects， which bother the clinicians and limit the further application.　Objective　This article reviews the scientific basis for the rational combination of opioids to improve analgesia and reduce side effects.　Content　we summarize the feasibility for the united application of opioids dissimilarly acting on different receptors， and elaborate the advancement in acute and chronic pain therapy.　Trend　More attention is paid to improving the curative effect and patient's satisfaction. The standardized and reasonable combination program would be prevailed in the treatment of acute and chronic pain.