There is growing interest in the potential for complex systems perspectives in evaluation. This reflects a move away from interest in linear chains of cause-and-effect, towards considering health as an outcome of interlinked elements within a connected whole. Although systems-based approaches have a long history, their concrete implications for health decisions are still being assessed. Similarly, the implications of systems perspectives for the conduct of systematic reviews require further consideration. Such reviews underpin decisions about the implementation of effective interventions, and are a crucial part of the development of guidelines. Although they are tried and tested as a means of synthesising evidence on the effectiveness of interventions, their applicability to the synthesis of evidence about complex interventions and complex systems requires further investigation. This paper, one of a series of papers commissioned by the WHO, sets out the concrete methodological implications of a complexity perspective for the conduct of systematic reviews. It focuses on how review questions can be framed within a complexity perspective, and on the implications for the evidence that is reviewed. It proposes criteria which can be used to determine whether or not a complexity perspective will add value to a review or an evidence-based guideline, and describes how to operationalise key aspects of complexity as concrete research questions. Finally, it shows how these questions map onto specific types of evidence, with a focus on the role of qualitative and quantitative evidence, and other types of information.