Opioid tolerance is a significant clinical phenomenon. Patients may develop opioid tolerance within several hours even after a single bolus of opioid. Animal studies have revealed that there were two kinds of opioid tolerance, namely acute opioid tolerance and chronic opioid tolerance. Acute opioid tolerance may develop within 4 hours after a single bolus of fentanyl or morphine, and 1 hour after a single injection of alfentanil. Chronic opioid tolerance may develop with an incubation period of 8-10 days and last for a long period. The characteristics of acute opioid tolerance may differ from those of chronic opioid tolerance. The mechanisms underlying acute and chronic opioid tolerance are not well studied and need to be further explored. However, in the future, the combined administration of delta opioid receptor antagonists or opioid agonist-antagonists along with opioid agonist (such as morphine) may not only provide less opioid tolerance but also maintain adequate analgesia in clinical practice.