© 2015, Biomedical Engineering Society. Spinal fusion is one of the most commonly performed procedures for the treatment of spinal instability caused by a multitude of pathologies. However, despite significant advances in spinal instrumentation, failed fusion, or pseudoarthrosis, remains a significant challenge. Therefore, other additives such as bone graft extenders and growth factors have been explored as a method to augment fusion rates. Platelet-rich plasma (PRP) represents an additional approach, as it has shown some promise in bone regeneration. While the general use of PRP in orthopedic applications has been reviewed previously, its use in spinal fusion has not been systematically analyzed. The objective of this review is to systematically discuss the role of PRP in augmentation of bone regeneration for the purpose of spinal fusion. Background information on PRP, including a discussion of its preparation, activation, and growth factors, is included. Additionally, data from in vitro studies utilizing PRP in bone tissue engineering strategies is analyzed, and the available animal and clinical studies are systematically reviewed in order to provide guidance on future research pathways as well as the potential role of PRP in spinal fusion surgery.