The trigeminal nerve is the great sensory nerve of the facial portion of the head, and an intimate knowledge of this nerve and its surrounding structures is a prerequisite to the application of profound local anesthesia without complication. In this review article, the classic description of the relevant anatomy is described and is updated with recently published research into anatomic variations that have an impact on the induction of clinical local anesthesia. Causes of both failure and complications of traditional local anesthetic techniques are explained, and recommendations for avoiding these pitfalls are made.