One of the important attempts in clinical oral surgery practice is to maintain safe and effective local anesthesia. Dental procedures are frequently performed under local anesthesia; thus, drug-related complications are often encountered. It is mandatory to have a preoperative evaluation of the patient and choosing the proper local anesthetic agent. Various complications including hypersensitivity, allergy, overdosage, toxicity, hematoma, trismus, paresthesia, or neuralgia can be observed during practice. Therefore, the practitioner should be aware of the possible complications and management methods. The aim of this chapter is to review the preoperative and postoperative complications associated with the local anesthetic in oral and maxillofacial surgery practice. The prevention of measures and treatment of the complications is also emphasized.