OBJECTIVES: This article outlines a research and development agenda for systematic reviews that ask complex questions about interventions varying in degree and type of complexity. STUDY DESIGN AND SETTING: Consensus development by key authors of articles on methodological challenges in systematic reviews of complex interventions, based on a 2-day workshop in Montebello, Canada, January 2012. RESULTS: There is an urgent need for a more precise and consistently applied lexicon and language to disaggregate several conceptually distinct dimensions of "complexity." Selected current evidence synthesis methods have potential application in reviews where complexity is important. There is a lack of evaluation of methods to better understand the nature of complex interventions and the optimal processes of synthesizing and interpreting evidence from these systematic reviews. Gaps in methods, knowledge, and know-how exist, and there is a need for additional guidance. CONCLUSION: Understanding how complexity can impact on findings of systematic reviews is critical. Experience in applying methods that have been developed to facilitate this understanding is limited, and the degree to which these approaches improve the systematic review process or transparency is only partially understood. Future research should concentrate on the impact of complexity on the systematic review process and findings and on further methodological development.