The choice of substrate(s) to use for bone grafting in spinal arthrodesis is complex. Numerous options exist to increase the likelihood of achieving a stable fusion. In addition to local bone and iliac crest bone graft, which is the gold standard for spinal surgery, multiple formulations are available to augment the volume of graft material and optimize the biochemical milieu for bone formation. Bone graft extenders, replacements, and enhancers all work to promote an environment that is favorable for growth. Bone morphogenetic protein, bone matrices, ceramics, and mesenchymal stem cells are commonly used substrates that have had a favorable effect on spinal surgery. Although nonautologous grafting materials can be advantageous, it is important to discuss with patients the risks inherent to each of these substances before their use in surgery.