Background context: The acceptance of spinal manipulation as a reasonable method of treating certain patients with spinal pain over the past decade has led to a renewed interest and increased use of these techniques performed in conjunction with commonly used medications and procedures. Manual therapy is increasingly being used in conjunction with anesthetics, sedatives or analgesics as well as local, epidural and intra-articular injections. Purpose: This report provides a review of the literature and presents a description of current clinical practice methods for the application of the different techniques of medication-assisted spinal manipulation therapy followed by a discussion of the current clinical support and the published indications, contraindications and complications for each of these procedures. Study design/setting: This technical report integrates a literature review with information gathered through personal interviews, review of medicine-assisted manipulation courses and observations of clinical procedures. Methods: A PubMed search from 1966 to the present was performed to identify appropriate articles concerning the combination of spinal manipulation therapy with such medical procedures as the use of anesthetic, conscious sedation, local injection of analgesic, anti-inflammatory and proliferant agents and intra-articular injections. Additional articles and information were gathered through review of pertinent references, attendance of various technique specific seminars and communication with experts familiar with these procedures. Results: Four categories of medication-assisted manipulation were identified: manipulation under general anesthesia or sedation, manipulation under epidural anesthesia with or without epidural steroid injection, manipulation under joint anesthesia/analgesia, and manipulation with injectants, such as steroids or proliferant agents. The literature consists primarily of case reports and case series with two randomized controlled trials and one cohort study. Conclusions: Medicine-assisted spinal manipulation therapies have a relatively long history of clinical use and have been reported in the literature for over 70 years. However, evidence for the effectiveness of these protocols remains largely anecdotal, based on case series mimicking many other surgical and conservative approaches for the treatment of chronic pain syndromes of musculoskeletal origin. There is, however, sufficient theoretical basis and positive results from case series to warrant further controlled trials on these techniques.