There are several different classes of synthetic dermal fillers and volume enhancers including semipermanent and permanent products available in the United States. Based on clinical and scientific evidence, this article reviews the chemical and polymeric properties, clinical data, patient selection, indications for use, injection technique, and adverse event profiles of permanent synthetic injectables currently used in clinical practice in the United States: medical-grade liquid injectable silicone and polymethyl methacrylate. Understanding the unique characteristics of these two products reinforces the advantages and disadvantages of each, including under what circumstances they should be used and why they perform the way they do.