Knowledge of paleo-atmospheric CO2 is critical to understanding how Earth System processes respond to a full range of CO2 concentrations, both past and future. This review addresses the terrestrial and marine proxies used to estimate paleo-CO2 concentrations and how the biological and/or geochemical properties of each proxy encodes the ambient CO2 signal, as well as the associated assumptions and uncertainties of the CO2 estimates. The Phanerozoic history of atmospheric CO2 is discussed, highlighting a new high-fidelity Cenozoic CO2 curve and its implications. Subsequently, pre-Cenozoic CO2 as is currently understood is outlined, in the context of its temporal relationship to climate and evolutionary changes. An overview of carbon cycle modeling for estimating paleo-CO2 is presented, including the key principles, models, and updates in the field, as well as the key emerging patterns and planned next steps. The review concludes by addressing next steps in advancing the science of CO2 reconstruction and for improving our understanding of the evolution of atmospheric CO2 over the past half-billion years.