Multiple meta-analyses have now documented small positive effects of teacher professional development (PD) on pupil test scores. However, the field lacks any validated explanatory account of what differentiates more from less effective in-service training. As a result, researchers have little in the way of advice for those tasked with designing or commissioning better PD. We set out to remedy this by developing a new theory of effective PD based on combinations of causally active components targeted at developing teachers’ insights, goals, techniques, and practice. We test two important implications of the theory using a systematic review and meta-analysis of 104 randomized controlled trials, finding qualified support for our framework. While further research is required to test and refine the theory, we argue that it presents an important step forward in being able to offer actionable advice to those responsible for improving teacher PD.