Understanding the anatomy and distribution of facial fat and the alterations that occur during the aging process is essential to effectively and precisely achieve facial rejuvenation. Over the past several years, through cadaveric dissections and computed tomographic studies, much has been discovered concerning the adipose tissue of the face and how it influences the dynamic process of aging. Site-specific augmentation with fillers can now be used to refine facial shape and topography in a more predictable and precise fashion. The purpose of this article is to provide an introduction to facial fat compartmentalization along with clinical examples to illustrate how the knowledge of underlying anatomy influences site-specific augmentation.