Despite the large volume of animal data regarding the use of synthetic bone graft substitutes or extenders, there are very few data regarding the use of these substances for fusion in lumbar degenerative disease. The best available data indicate that rhBMP-2 is a viable alternative to autograft bone for interbody fusion procedures. This same substance may also be a viable alternative to autograft for PLF; however, definitive medical evidence is not yet available. There is little, if any, medical evidence to support the use of other biological agents at the present time. As promising new compounds are brought to market, well-designed cohort studies and randomized trials will be required to determine the actual usefulness of these compounds in clinical practice. It is important not to generalize the results obtained with one preparation or application to different preparations or applications. The use of synthetic calcium phosphate ceramics as graft extenders appears to be reasonable in certain situations. The medical evidence available regarding their use is limited and of poor quality. Further study will be required to establish their utility for use in spinal fusion.