Background: Current evidence shows that manual therapy elicits analgesic effect in different populations (healthy, pain inflicted and patients with musculoskeletal pain) when carried out at the spinal column, although the clinical significance of these effects remains unclear. Also the analgesic effects of manual therapy on peripheral joints have not been systematically reviewed. Methods: A systematic review was carried out following the PRISMA-guidelines. Manual therapy was defined as any manual induced articular motion with the aim of inducing analgesic effects. Outcome measure was pain threshold. Results: A total of 13 randomized trials were included in the review. In 10 studies a significant effect was found. Pressure pain thresholds increased following spinal or peripheral manual techniques. In three studies both a local and widespread analgesic effect was found. No significant effect was found on thermal pain threshold. Discussion: Moderate evidence indicated that manual therapy increased local pressure pain thresholds in musculoskeletal pain, immediately following the intervention. No consistent result was found on remote pressure pain threshold. No significant changes occured on thermal pain threshold values. The clinical relevance of these effects remains contradictory and therefore unclear. (C) 2014 Elsevier Ltd. All rights reserved.