Healing and fusion in challenging bone grafting procedures is not guaranteed using the gold standard of autogenous iliac crest bone, and clinicians are increasingly interested in tissue engineering solutions using cells and signaling factors to enhance both overall success rate and time to fusion. The potential role in wound repair from application of cytokines contained in platelets was initially described more than 20 years ago. A rapid, simple preparation method to perioperatively separate and collect the platelet-rich fraction was developed a decade later, expanding the potential range of clinical applications. Numerous additional point-of-care techniques have since been introduced, potentially providing a cost-effective alternative to single recombinant proteins. As with many emerging technologies, clinicians are confronted with a frequently conflicting array of largely anecdotal claims for clinical utility. With a focus on structural bone graft repair, this chapter will present the therapeutic basis for clinical use of topically applied autogenous growth factor preparations and summarize existing experimental and application-specific clinical outcomes reports.