Midface rejuvenation is a highly beneficial procedure to improve facial aesthetics. The usage of hyaluronic acid dermal fillers, for enhancing the projection of the cheekbones by adding volume to the upper cheeks significantly contributes to a more youthful appearance. Hyaluronic acid fillers have undergone significant advancements in the last 20 years to address specific therapeutic requirements, including enhanced projection capability and the ability to accomodate facial movements. Consequently, they have become the preferred method for midface rejuvenation across all age groups. They afford noninvasive treatment, fast outcomes, and low recovery time. Injecting the midface area can inadvertently negatively emphasise other cosmetic concerns, such as infraorbital hollowing and nasolabial folds, due to the significant role played by the 5-layered structure of the midface in shaping the human face. However, midface rejuvenation necessitates a customized treatment strategy and a comprehensive understanding of anatomy to reduce procedural risks and obtain natural results. This chapter aims to offer a detailed anatomical description of the midface and the typical path and depth of blood vessels in the surrounding area. This information will help define a treatment area and reduce the chances of complications during procedures. In addition, we suggest a treatment algorithm to address the varying mobility and mechanical limitations of each layer of the midface. This algorithm aims to tailor the treatment strategy to the individual characteristics of each patient, such as their age, gender, skin type, and facial structure.