Anatomical descriptions usually include only the average topographical relationships, but the anatomical structures particularly in the head region display great variability. This is one of the essential causes underlying side effects and complications of local dental anesthesia. In examinations of intravascular needle placement in over 6000 local anesthetic injections in the jaws, positive blood aspiration occurred most frequently (5.8%) at the mandibular foramen. The close proximity to the cerebral vessels explains the frequency of severe side effects. Anatomical studies on the course of the maxillary artery and its branches as well as the course of the nerve demonstrate that unexpected anatomical constellations can lead to both anesthetic failure and dramatic side effects.