The use of botulinum toxin in the lower face is more complex and less reliable than its use in the upper face. Use in the lower face is also fraught with more adverse events. The anatomy of the lower face is complex, as the muscles of this region are very close together and interface at different levels and depths to perform heterogeneous functions, such as talking, eating, drinking, and expressivity of the face. This article, based on the anatomical knowledge of each muscle of the lower face, provides recommendations and guidelines to perform botulinum toxin injection safely. The review of each muscle with its relevant anatomy and relationship of this three-dimensional anatomy with the cutaneous plane gives the exact position of injectable locations. For each muscle, the number of points related to the motor end plate location and the exact dose related to the muscular mass are indicated. Summary tables are provided.