With the growth of the understanding of opioids and the improvement of enhanced recovery after surgery (ERAS), more and more patients have been used opioid‑free anesthesia (OFA). OFA is multimodal anesthesia associating drugs and/or techniques that allow a good quality general anesthesia with no need for opioids. Some case reports and studies are showing that OFA is feasible and safe and decreases the risk of common opioid‑relative adverse effects. This article reviews the definite, benefits and indications of OFA, selection of analgesic drugs (dexmedetomidine, ketamine, lidocaine, magnesium sulfate, anti‑inflammatory drugs, etc), and methods of anesthesia. OFA as a new paradigm, there is a need for more research on benefits and both early and long‑term outcome after surgery. To support the clinic routine use of OFA has still a debate.