Spinal manipulation is an intervention performed on synovial joints of the spine, including the z-joints, the atlanto-occipital, atlanto-axial, lumbosacral, sacroiliac, costotransverse and costovertebral joints. It is typically applied with therapeutic intent, most commonly for the treatment of low back pain.

Clinical guidelines from different countries come to different conclusions with respect to spinal manipulation.

A 2012 Cochrane review found that spinal manipulation was as effective as other commonly used therapies. A 2010 systematic review found that most studies suggest SM achieves equal or superior improvement in pain and function compared with other commonly used interventions for short-, intermediate-, and long-term follow-up. A 2019 systematic review concluded that SM produced comparable results to recommended treatments for chronic low back pain, while SM appeared to give improved results over non-recommended therapies for short-term functional improvement.

In 2007, the American College of Physicians and the American Pain Society jointly recommended that clinicians consider spinal manipulation for patients who do not improve with self-care options, and the Clinical Guideline Committee for the American College of Physicians updated the guideline in 2017 to include that non-pharmacological approaches to pain management should be considered, however, that there is only low-quality evidence supporting effectiveness of spinal manipulation. Reviews published in 2008 and 2006 suggested that SM for low back pain was equally effective as other commonly used interventions. A 2007 literature synthesis found good evidence supporting SM and mobilization for low back pain. Of four systematic reviews published between 2000 and 2005, one recommended SM and three stated that there was insufficient evidence to make recommendations. A 2017 review concludes "for patients with nonchronic, nonradicular LBP, available evidence does not support the use of spinal manipulation or exercise therapy in addition to standard medical therapy."

For neck pain, manipulation and mobilization produce similar changes, and manual therapy and exercise are more effective than other strategies. A 2015 Cochrane systematic review found that there is no high-quality evidence assessing the effectiveness of spinal manipulation for treating neck pain. Moderate-to-low-quality evidence suggests that multiple spinal manipulation sessions may provide improved pain relief and an improvement in function when compared to certain medications. Due to the potential risks associated with spinal manipulation, high-quality randomized controlled trials are needed to determine the clinical role of spinal manipulation. A 2007 systematic review reported that there is moderate- to high-quality evidence that subjects with chronic neck pain, not due to whiplash and without arm pain and headaches, show clinically meaningful improvements from a course of spinal manipulation or mobilization. There is not enough evidence to suggest that spinal manipulation is an effective long-term treatment for whiplash, but there are short-term benefits.

Historically, some within the chiropractic profession have claimed that spinal adjustments have physiological effects on visceral functions and thus affect overall health beyond musculoskeletal conditions. This view originated in the 19th century with Daniel David Palmer's original thesis that subluxations caused many diseases. Over time, this hypothesis is inconsistent with our modern understanding of pathology and disease, and only "a small proportion of chiropractors, osteopaths, and other manual medicine providers use[ing] spinal manipulative therapy (SMT) to manage non-musculoskeletal disorders. However, the efficacy and effectiveness of these interventions to prevent or treat non-musculoskeletal disorders remain controversial."

A 2019 global summit of "50 researchers from 8 countries and 28 observers from 18 chiropractic organizations" conducted a systematic review of the literature, and 44 of the 50 "found no evidence of an effect of SMT for the management of non-musculoskeletal disorders including infantile colic, childhood asthma, hypertension, primary dysmenorrhea, and migraine. This finding challenges the validity of the theory that treating spinal dysfunctions with SMT has a physiological effect on organs and their function."

As for manipulation with the assistance of medication or anesthesia, a 2013 review concludes that the best evidence lacks coherence to support its use for chronic spine pain.