The anatomy of the eyelids and periorbital region is delicate. The individual anatomic variations determine each person’s eyelid appearance and function. It is essential that every surgeon that evaluates and treats the aesthetic conditions of patients desiring periorbital enhancement understands the association of anatomy and diagnosis. Each periorbital aesthetic diagnosis has an anatomic basis, and knowledge of the applied anatomy allows a targeted treatment plan. This article outlines the layered anatomy with its clinical significance for the eyelids and periorbital region. Specific examples are used to illustrate the applied anatomy. A contemporary treatment plan for each anatomic problem is given.