Soft tissue filler procedures have increased dramatically in popularity in the United States. Synthetic fillers such as calcium hydroxyapatite (CaHA), polymethyl methacrylate (PMMA), and poly-l-lactic acid (PLLA), and silicone provide initial volume replacement but have an additional biostimulatory effect to supplement facial volumization. Indications include human immunodeficiency virus lipoatrophy and nasolabial folds for CaHA and PLLA and atrophic acne scars for PMMA. Most clinical use of these synthetic fillers is in an off-label fashion. Beyond the proper choice of a synthetic filler, careful consideration of dilution, injection method, and postprocedural care allows for successful and consistent results.