Recently, peripheral nerve blocks are extensively applied for many patients undergoing surgical or nonsurgical analgesia. However, the effectiveness is limited by the duration of action of local anesthetics. Therefore, the application of adding local anesthetic adjuvants is evolved to prolong the duration of analgesia and decrease the concentration of local anesthetics in peripheral nerve blocks. There are many local anesthetic adjuvants available such as morphine, fentanyl, sufentanil, hydromorphone, and buprenorphine, dexmedetomidine, dexamethasone, midazolam, and magnesium sulfate. Most of them are safe and possess little adverse effects, while none of them is acknowledged by the food and drug administration. Therefore, this review is aimed to delineate benefits and adverse effects for clinical anesthesia.