The locoregional anesthesia has been administrated in dentistry for more than 100 years, being essential for pain management. Almost every dental procedure requires a temporary sensory loss of hard or soft tissues of the oral cavity. The aim of this chapter is to emphasize the most relevant aspects of locoregional anesthesia in dentistry, specifically related to anesthesia evolution over the decades, clinical anatomy, differences between plexus and peripheric troncular anesthesia techniques, risk patients for local anesthesia administration, complications, trypanophobia, problems in achieving local anesthesia and new perspectives. This complex chapter presents up-to-date information in a clear and concise manner, that can be useful for students, dentists, for oral and maxillofacial surgeons. The detailed knowledge presented in the next pages along with the schematic figures can be used for a better understanding of the local anesthesia and help the practitioner to obtain a complete anesthesia of the territory of interest.