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The aging process affects every anatomical layer of the face. Improved knowledge of how aging occurs in each anatomical layer of the face has helped evolve the facial rejuvenation strategies with HA fillers. Understanding the age-related changes in the anatomical facial layers, including their time of onset and how the changes occur in the different tissue layers, an injector can provide much more targeted and refined HA filler treatments. As fillers’ use has increased, there has been a distinct shift away from procedures lifting the skin and SMAS. We can selectively target the anatomical facial layers with HA fillers for more refined and predictable outcomes. An extensive range of HA filler variants is now available. Each filler type is optimized and designed to be injected into specific tissue planes for the best results. Knowing the predictable aging changes in the different tissue layers of the face is crucial as this guides the optimum filler choice. Working knowledge of the individual characteristics of the numerous HA-based products allows for their effective placement in the correct layer. Familiarity with the correct HA product may also help to minimize the downtime and risk of adverse events.