The ideal soft-tissue filler for wrinkles and skin defects should be safe, biocompatible, resistant to phagocytosis, persist and maintain its volume without being resorbed or degraded. ArteFill®, an improved, next-generation derivative of Artecoll®, is expected to become the first and only FDA-approved permanent filler for use in the USA in 2006 and will be available worldwide. ArteFill consists of polymethylmethacrylate microspheres suspended in a 3.5% solution of bovine collagen containing 0.3% lidocaine. In this article, the pathophysiology, efficacy and safety of ArteFill are discussed and details of its injection technique are provided. Insight into the pharmacoeconomic value of ArteFill over nonpermanent fillers and ArteFill's unique role in the growing world market of dermal fillers is provided.