Restoring volume in the middle and lower portions of the face is becoming an indispensable component of modern facial rejuvenation. Radiesse (BioForm Medical, San Mateo, Calif.) is an injectable filler material composed of synthetic calcium hydroxylapatite microspheres (30 percent) suspended in an aqueous carrier gel (70 percent). At present, Radiesse is indicated in the United States for correction of moderate to deep nasolabial folds and for correction of the signs of facial fat loss (lipoatrophy) in people with human immunodeficiency virus. Its off-label use in other facial aesthetic indications is widely reported in the literature. The ability of Radiesse to provide immediate and durable effects has fueled interest in its use for expanded aesthetic applications, particularly in the middle and lower face. The authors’ consensus panel, consisting of a cross-section of experts in plastic surgery, facial plastic surgery, and dermatology, was convened to review the scientific literature and compare clinical experiences regarding the use of calcium hydroxylapatite. This report describes the characteristic effects of aging in the middle and lower face and reviews the composition of calcium hydroxylapatite, its safety and durability, and its appropriate use in a variety of facial applications, including nasolabial folds, correction of human immunodeficiency virus–associated lipoatrophy, augmentation of the malar, submalar, and zygomatic regions, and correction of oral commissure defects, marionette lines, and prejowl sulcus. Recommendations for Radiesse use in each area, including anesthesia, and injection techniques are provided. Measures for enhancing patient comfort, anticipating and minimizing potential complications, and optimizing aesthetic results are also discussed.