The objective of this study was to assess the evidence for or against the effectiveness of moxibustion as a treatment option for pain. Fourteen electronic databases were searched. Randomized clinical trials (RCTs) testing moxibustion in human patients with pain of any type were considered. Trials using direct or indirect moxibustion were included. Studies comparing moxibustion with other treatments of unproven effectiveness, studies testing moxibustion together with other treatments of unproven efficacy and trials where pain was not a central symptom of the condition were all excluded. The selection of studies, data extraction, and validation were performed independently by two reviewers. Four RCTs met all the inclusion criteria. Others were of poor methodological quality. Two RCTs suggested significant pain reductions for indirect moxibustion in osteoarthritis as compared with drug therapy (n = 200, RR, 1.11; 95% CI of 1.02 to 1.21, p = 0.02, heterogeneity: chi2 = 1.03, p = 0.31, I2 = 3%). The other two RCTs suggested positive effects of indirect or direct moxibustion on pain in scleroma or herpes zoster compared to drug therapy, respectively. We conclude that few RCTs are available that test the effectiveness of moxibustion in the management of pain, and most of the existing trials have a high risk of bias. Therefore, more rigorous studies are required before the effectiveness of moxibustion for the treatment of pain can be determined.