Background: The use of spinal manipulation (SM) for upper limb pain has been advocated based on the concept of regional interdependence. However, its evidence has not been established. Objective: To determine the level of evidence for the effectiveness of SM in patients with upper limb pain as part of the concept of regional interdependence. Methods: MeSH and Key words representing two broad subject areas: SM and upper limb disorders were used to conduct an electronic search in sixteen electronic databases. Randomized controlled trials and/or controlled clinical trials investigating the effects of SM in patients with upper limb pain were included. Studies including pain in the neck or scapular region and those using spinal mobilization were excluded. Meta-analysis was conducted to examine the effects of SM on upper limb pain. The overall quality of evidence was assessed using the GRADE system. Results: Out of 3307 studies, six trials met inclusion criteria for this review. Of these, three studies were included in meta-analysis. Meta-analysis results suggested there were no statistical differences between SM and other interventions in the effects on reducing upper limb pain. The overall quality of evidence was very low. Conclusion: The number of studies regarding the current topic is limited. There is very low quality evidence that SM is not better nor inferior than other interventions in the management of upper limb pain.