Objective: Goal setting is a common feature of behavior change interventions, but it is unclear when goal setting is optimally effective. The aims of this systematic review and meta-analysis were to evaluate: (a) the unique effects of goal setting on behavior change, and (b) under what circumstances and for whom goal setting works best. Method: Four databases were searched for articles that assessed the unique effects of goal setting on behavior change using randomized controlled trials. One-hundred and 41 papers were identified from which 384 effect sizes (N = 16,523) were extracted and analyzed. A moderator analysis of sample characteristics, intervention characteristics, inclusion of other behavior change techniques, study design and delivery, quality of study, outcome measures, and behavior targeted was conducted. Results: A random effects model indicated a small positive unique effect of goal setting across a range of behaviors, d = .34 (CI [.28, .41]). Moderator analyses indicated that goal setting was particularly effective if the goal was: (a) difficult, (b) set publicly, and (c) was a group goal. There was weaker evidence that goal setting was more effective when paired with external monitoring of the behavior/outcome by others without feedback and delivered face-to-face. Conclusions: Goal setting is an effective behavior change technique that has the potential to be considered a fundamental component of successful interventions. The present review adds novel insights into the means by which goal setting might be augmented to maximize behavior change and sets the agenda for future programs of research.