Back and neck pain are major health problems that are leading causes of years lived with disability and significant sources of societal burden due to their associated direct (e.g., health care costs directly related to the treatment of neck or back pain) and indirect costs (e.g., costs resulting from loss of productivity). The one-year prevalence of low back pain is estimated at 38%, while estimates for the one-year prevalence of neck pain range between 30% and 50%. Although a proportion of individuals with back or neck pain may recover over a short period of time, many will experience chronic pain that may last months or years. The duration of pain is used to classify an individual’s condition as either acute (symptoms lasting less than 12 weeks) or chronic (symptoms lasting more than 12 weeks). Common causes of back or neck pain include disk herniation, muscle strains, compression fracture, lumbar and cervical spinal stenosis or other forms of nerve compression, whiplash, sciatica, osteoarthritis, and spondylolisthesis. Though back and neck pain may differ in their affected region and underlying etiologies, individuals who report symptoms of either condition may be offered similar therapeutic options. Pharmacological interventions include acetaminophen, non-steroidal anti-inflammatory drugs, opioids, systemic corticosteroids, and skeletal muscle relaxants. Non-pharmacological interventions include exercise, psychological therapies, patient education, multidisciplinary rehabilitation, acupuncture, transcutaneous electrical nerve stimulation, and manual therapy. Despite these numerous options, the long-term efficacy and safety of many interventions for the treatment of back and neck pain is not well-established. Manual therapy is a physical treatment applied by skilled clinicians (e.g., physiotherapists, chiropractors, osteopaths) that directly or indirectly targets a variety of anatomical structures of the musculoskeletal system. The goal of manual therapy is to increase range of motion, improve tissue extensibility, induce relaxation, modulate pain, and reduce swelling or inflammation. Manual therapy constitutes a wide variety of different techniques, such as: manipulation, mobilization, traction, and soft-tissue therapies (e.g., massage). CADTH has conducted a series of reports regarding the use of manual therapy for neck or lower back pain. Two CADTH reports, published in 2017, reviewed the evidence for neck and lower back pain separately. The current report will update components of these previous CADTH reports by summarizing the evidence regarding the clinical effectiveness of manual therapy for persistent or chronic non-cancer back and neck pain published since 2017.