The duration of action of commonly used traditional long‑acting local anesthetics often fails to cover the duration of postoperative pain. To enhance patient comfort and alleviate a series of issues related to pain during the perioperative period, the development of new ultra‑long‑acting local anesthetics is particularly important. This article will introduce the clinical and basic research progress on ultra‑long‑acting local anesthetics based on different controlled release systems, revealing their advantages and disadvantages in terms of analgesic duration and safety, in order to provide reference for future perioperative analgesia strategies.