Spinal manipulation (SMT) is commonly used for treating individuals experiencing musculoskeletal pain. The mechanisms of SMT remain unclear; however, pain sensitivity testing may provide insight into these mechanisms. The purpose of this systematic review is to examine the literature on the hypoalgesic effects of SMT on pain sensitivity measures and to quantify these effects using meta-analysis. We performed a systematic search of articles using CINAHL, MEDLINE, PsycINFO, and SPORTDiscus from each databases' inception until May 2011. We examined methodological quality of each study and generated pooled effect size estimates using meta-analysis software. Of 997 articles identified, 20 met inclusion criteria for this review. Pain sensitivity testing used in these studies included chemical, electrical, mechanical, and thermal stimuli applied to various anatomical locations. Meta-analysis was appropriate for studies examining the immediate effect of SMT on mechanical pressure pain threshold (PPT). SMT demonstrated a favorable effect over other interventions on increasing PPT. Subgroup analysis showed a significant effect of SMT on increasing PPT at the remote sites of stimulus application supporting a potential central nervous system mechanism. Future studies of SMT related hypoalgesia should include multiple experimental stimuli and test at multiple anatomical sites.