The dramatic growth of Web 2.0 technologies and online social networks offers immense potential for the delivery of health behavior change campaigns. However, it is currently unclear how online social networks may best be harnessed to achieve health behavior change. The intent of the study was to systematically review the current level of evidence regarding the effectiveness of online social network health behavior interventions. Eight databases (Scopus, CINAHL, Medline, ProQuest, EMBASE, PsycINFO, Cochrane, Web of Science and Communication & Mass Media Complete) were searched from 2000 to present using a comprehensive search strategy. Study eligibility criteria were based on the PICOS format, where 'population' included child or adult populations, including healthy and disease populations; 'intervention' involved behavior change interventions targeting key modifiable health behaviors (tobacco and alcohol consumption, dietary intake, physical activity, and sedentary behavior) delivered either wholly or in part using online social networks; 'comparator' was either a control group or within subject in the case of pre-post study designs; 'outcomes' included health behavior change and closely related variables (such as theorized mediators of health behavior change, eg, self-efficacy); and 'study design' included experimental studies reported in full-length peer-reviewed sources. Reports of intervention effectiveness were summarized and effect sizes (Cohen's d and 95% confidence intervals) were calculated wherever possible. Attrition (percentage of people who completed the study), engagement (actual usage), and fidelity (actual usage/intended usage) with the social networking component of the interventions were scrutinized. A total of 2040 studies were identified from the database searches following removal of duplicates, of which 10 met inclusion criteria. The studies involved a total of 113,988 participants (ranging from n=10 to n=107,907). Interventions included commercial online health social network websites (n=2), research health social network websites (n=3), and multi-component interventions delivered in part via pre-existing popular online social network websites (Facebook n=4 and Twitter n=1). Nine of the 10 included studies reported significant improvements in some aspect of health behavior change or outcomes related to behavior change. Effect sizes for behavior change ranged widely from -0.05 (95% CI 0.45-0.35) to 0.84 (95% CI 0.49-1.19), but in general were small in magnitude and statistically non-significant. Participant attrition ranged from 0-84%. Engagement and fidelity were relatively low, with most studies achieving 5-15% fidelity (with one exception, which achieved 105% fidelity). To date there is very modest evidence that interventions incorporating online social networks may be effective; however, this field of research is in its infancy. Further research is needed to determine how to maximize retention and engagement, whether behavior change can be sustained in the longer term, and to determine how to exploit online social networks to achieve mass dissemination. Specific recommendations for future research are provided.