Over 700,000 osteoporotic compression fractures occur each year in the United States, twice the number of hip fractures. These vertebral fractures, most of which occur in the elderly, represent significant personal and societal burdens. Percutaneous vertebroplasty (PVP) is a minimally invasive method that involves the percutaneous injection of polymethylmethacrylate (PMMA) into a collapsed vertebral body to stabilize the vertebra. Kyphoplasty is an advanced minimally invasive technique with a number of potential advantages over PVP, including lower risk of cement extravasation and better restoration of vertebral body height and spinal biomechanics. The filling materials used for both these techniques require good biocompatibility, good biomechanical strength and stiffness, and good radiopacity for the fluoroscopy guided procedures. New filler materials (synthetic bone substitutes, e.g., composite resin materials, calcium phosphate or calcium sulfate cements) in addition to new PMMA formulations are now available for clinical use. In this review paper, we will focus on the issues and characteristics of these filler materials as they pertain to vertebral augmentation procedures.