Paleo-CO2 reconstructions are integral to understanding the evolution of Earth system processes and their interactions given that atmospheric CO2 concentrations are intrinsically linked to planetary function. Furthermore, past periods of major climate change provide unique insights into the response of land-atmosphere-ocean interactions to warming induced climate change, in particular for times of pCO2 comparable to those projected for our future. How well the past can inform the future, however, depends on how well paleo-CO2 estimates are constrained. In this talk, I will first discuss approaches to reconstructing paleo-CO2 concentrations, the challenges of constraining the uncertainty of these estimates, and the implications for constraining critical issues such as climate sensitivity. I will introduce a new community initiative, CO2PIP, focused on advancing the reconstruction of paleo-CO2 through modernizing of existing records and quantifying the representation of CO2 proxy sensitivities to environmental and ecophysiological conditions and processes that govern the CO2 signals. I will then focus on a deep-time glaciated period (the late Paleozoic Ice Age), characterized by pCO2 fluctuations within the range of Quaternary levels to those projected by socio-economic emission scenarios of this century, as well as defined by CO2-driven abrupt warmings that led to major changes in environmental conditions in the oceans and on land. An integrated multi-proxy data-modeling approach to investigating this deep-time icehouse provides a framework to evaluate the mechanistic linkages between processes and to conceptualize the collective data set. It further reveals the underlying processes linking pCO2 and environmental changes and documents the sensitivity of Earth System modeled atmospheric and oceanic circulation to changing pCO2. Application of paleo-CO2 and fossil plant morphologic and biogeochemical data to process-based ecosystem modeling documents physiological responses to CO2 and suggests ecosystem-scale vegetation-climate-CO2 feedbacks that would have influenced water cycling, surface runoff and weatherability, and led to major changes in organic carbon burial, and in turn atmospheric pCO2.