Study design: Systematic literature review and meta-analysis. Objective: In symptomatic subjects to: (1) examine the effects of a single session of joint mobilization on pain at rest and with most painful movement, and (2) compare the effects when joint mobilization is provided to a specific or non-specific spinal level. Background: Joint mobilization is routinely used for treating spinal pain in conjunction with other interventions, but its unique effect is not well understood. Further, there is controversy about the role of 'specific level' techniques in producing benefit. Methods: Searches were performed for randomized controlled trials (RCTs) using electronic databases (MEDLINE, CINAHL, and PEDro) from 1966 through November 2010. Methodological quality was assessed using previously detailed criteria. Meta-analysis and meta-regression were conducted on eligible studies. Results: Eight RCTs with a mean methodological score of 10/12 were included. Significant heterogeneity (P50.075) was found in the overall meta-analysis estimate. When stratified by body location, no significant individual effect was found for pain at rest. However, there was a statistical mean difference [0.71 (95% confidence interval: 0.13-1.28)] between pain at rest for the cervical and lumbar individual means. Conclusions: We found multiple studies which provided evidence that a single session of joint mobilization can lead to a reduction of pain at rest and with most painful movement. When using joint mobilization, the need for specific versus non-specific level mobilization may be influenced by anatomical region; the direction of effect in the cervical spine was toward specific mobilization and in the lumbar spine towards non-specific mobilization.