ConspectusCarbon capture, utilization, and storage have been identified as key technologies to decarbonize the energy and industrial sectors. Although postcombustion CO2 capture by absorption in aqueous amines is a mature technology, the required high regeneration energy, losses due to degradation and evaporation, and corrosion carry a high economic cost, precluding this technology to be used today at the scale required to mitigate climate change. Solid adsorbent-based systems with high CO2 capacities, high selectivity, and lower regeneration energy are becoming an attractive alternative for this purpose. Conscious of this opportunity, the search for optimal adsorbents for the capture of CO2 has become an urgent task. To accurately assess the performance of CO2 separation by adsorption at the needed scale, adsorbents should be synthesized and fully characterized under the required operating conditions, and the proper design and simulation of the process should be implemented along with techno-economic and environmental assessments. Several works have examined pure CO2 single-component adsorption or binary mixtures of CO2 with nitrogen for different families of adsorbents, primarily addressing their CO2 adsorption capacity and selectivity; however, very limited data is available under other conditions and/or with impurities, mainly due to the intensive experimental (modeling) efforts required for the large number of adsorbents to be studied, posing a challenge for their assessment under the needed conditions. In this regard, molecular simulations can be employed in synergy with experiments, reliably generating missing adsorption properties of mixtures while providing understanding at the molecular level of the mechanism of the adsorption process.This Account provides an outlook on strategies used for the rational design of materials for CO2 capture from different sources from the understanding of the adsorption mechanism at the molecular level. We illustrate with practical examples from our work and others' work how molecular simulations can be reliably used to link the molecular knowledge of novel adsorbents for which limited data exist for CO2 capture adsorption processes. Molecular simulation results of different adsorbents, including MOFs, zeolites, and carbon-based and silica-based materials, are discussed, focusing on understanding the role of physical and chemical adsorption obtained from simulations and quantifying the impact of impurities in the performance of the materials. Furthermore, simulation results can be used for screening adsorbents from basic key performance indicators, such as cycling the working capacity, selectivity, and energy requirement, or for feeding detailed dynamic models to assess their performance in swing adsorption processes on the industrial scale, additionally including monetized performance indicators such as operating expenses, equipment sizes, and compression cost. Moreover, we highlight the role of molecular simulations in guiding strategies for improving the performance of these materials by functionalization with amines or creating hybrid solid materials. We show how integrating models at different scales provides a robust and reliable assessment of the performance of the adsorbent materials under the required industrial conditions, rationally guiding the search for best performers. Trends in additional computational resources that can be used, including machine learning, and perspectives on practical requirements for leveraging CO2 capture adsorption technologies on the needed scale are also discussed.