BACKGROUND: The Cochrane Collaboration has been at the forefront of developing methods for knowledge synthesis internationally. OBJECTIVES: We discuss three approaches to synthesize evidence for healthcare interventions: systematic reviews (SRs), overviews of reviews and comparative effectiveness reviews. METHODS: We illustrate these approaches with examples from knowledge syntheses on interventions for bronchiolitis, a common acute paediatric condition. Some of the differences among these approaches are subtle and methods are not necessarily mutually exclusive to a single review type. RESULTS AND CONCLUSIONS: Systematic reviews bring together evidence from multiple studies in a rigorous fashion for a single intervention or group of interventions. Systematic reviews, as they have developed within healthcare, often focus on single or select interventions and direct pairwise comparisons; therefore, end-users may need to read several individual SRs to inform decision making. Overviews of reviews compile information from multiple SRs relevant to a single health problem. Overviews provide the end-user with a quick overview of the available evidence; however, overviews are dependent on the methods and decisions employed at the SR level. Furthermore, overviews do not often integrate evidence from different SRs quantitatively. Comparative effectiveness reviews, as we define them here, synthesize relevant evidence from individual studies to describe the relative benefits (or harms) of a range of interventions. Comparative effectiveness reviews may use statistical methods (network meta-analysis) to incorporate direct and indirect evidence; therefore, they can provide stronger inferences about the relative effectiveness (or safety) of interventions. While potentially more expensive and time-consuming to produce, a comparative effectiveness review provides a synthesis of a range of interventions for a given condition and the relative efficacy across interventions using consistent and standardized methodology.