We discuss a strategy for investigating the impacts of climate change on Earth’s physical, biological and human resources and links to their socio-economic consequences. The features of the integrated global system framework that allows a comprehensive evaluation of climate change impacts are described with particular examples of effects on agriculture and human health. We argue that progress requires a careful understanding of the chain of physical changes—global and regional temperature, precipitation, ocean acidification and polar ice melting. We relate those changes to other physical and biological variables that help people understand risks to factors relevant to their daily lives—crop yield, food prices, premature death, flooding or drought events, land use change. Finally, we investigate how societies may adapt, or not, to these changes and how the combination of measures to adapt or to live with losses will affect the economy. Valuation and assessment of market impacts can play an important role, but we must recognize the limits of efforts to value impacts where deep uncertainty does not allow a description of the causal chain of effects that can be described, much less assigned a likelihood. A mixed approach of valuing impacts, evaluating physical and biological effects, and working to better describe uncertainties in the earth system can contribute to the social dialogue needed to achieve consensus—where it is needed—on the level and type of mitigation and adaptation actions that are required.