BACKGROUND AND OBJECTIVE: Advanced analytic methods for synthesizing evidence about complex interventions continue to be developed. In this paper, we emphasize that the specific research question posed in the review should be used as a guide for choosing the appropriate analytic method. METHODS: We present advanced analytic approaches that address four common questions that guide reviews of complex interventions: (1) How effective is the intervention? (2) For whom does the intervention work and in what contexts? (3) What happens when the intervention is implemented? and (4) What decisions are possible given the results of the synthesis? CONCLUSION: The analytic approaches presented in this paper are particularly useful when each primary study differs in components, mechanisms of action, context, implementation, timing, and many other domains.