Chronic pain is considered epidemic coupled with claims of inadequate treatment. While the understanding of pain, including diagnosis and treatment, is in its infancy, significant progress has been made with diagnostic and therapeutic interventional techniques during the past two decades. Though the structural basis of spinal pain is well established, some patients continue to present a diagnostic and therapeutic challenge. In addition to target-specific fluoroscopically guided techniques, Regenerative Injection Therapy (RIT), also known as prolotherapy, is a viable treatment in managing chronic spinal pain. Proponents suggest effectiveness of RIT in treating musculoskeletal pain, while opponents suggest otherwise. Multiple published studies show (RIT) is effective despite continued controversy. This review will describe various aspects of regenerative injection therapy, technical aspects and clinical effectiveness.