Biosphere reserves aim to reconciliate social and economic development with biodiversity conservation through complex spatial and governance arrangements. However, there is a generalized lack of information about how biosphere reserves are being managed and governed, and at what point their goals are being achieved, which limits a better understanding of the factors influencing biosphere reserve management effectiveness. Building on a systematic review of existing empirical studies, we developed a framework that identifies the main features related to biosphere reserve management effectiveness. We identified four main categories—context, inputs, process and outcomes—and 53 sub-categories, which interact at different scales and shape biosphere reserve effectiveness. We found that the capacity of biosphere reserves to achieve their goals is not only related to the way they are managed/governed, or to the inputs invested, but to many social and ecological contextual factors. We also identified benefits and impacts that were associated to biosphere reserves around the world. Comparing to other social–ecological system frameworks, ours provides a more inclusive approach, since it integrates the findings of studies with different research perspectives, considers a plurality of values attributed to natural resources, and the social–ecological system’s scales dynamics.