Effective and safe pain management during a third molar extraction is crucial to completing the treatment successfully and getting patient satisfaction. The inferior alveolar nerve block (IANB) and local infiltration anaesthesia are the most common injection techniques used for the extraction of mandibular third molars and other procedures performed on the lower molars. However, reports of the success rate of IANB vary significantly among studies, ranging from 23%, by using 2.2 ml of 2% lidocaine with 1:100,000 epinephrine for treating irreversible pulpitis on mandibular premolars or molars, to 92% by using 1.8 ml of 2% lidocaine with 1:100,000 epinephrine for anaesthetizing healthy mandibular second molars. This relatively high failure rate of IANB has been related to numerous factors, including operational errors, anatomical variations, infection, inflammation, pathological conditions, and psychological aspects such as fear, stress, and anxiety. According to Al Hindi et al. (2016), poor technique and anatomical variations are the primary cause of IANB failure. Therefore, in this chapter, we review the proper techniques for delivering inferior alveolar nerve anaesthesia for mandibular third molar extraction, emphasizing the importance of knowing the anatomy of the region to be anesthetized and the properties of local anaesthetic drugs used in dentistry.