AbstractIn recent decades, a microscopic understanding of solute–solvent intermolecular interactions has been key to advances in technologies based on supercritical carbon dioxide. In many cases, computational work has provided the impetus for new discoveries, shedding new light on important concepts such as the local structure around the solute in the supercritical medium, the influence of the peculiar properties of the latter on the molecular behavior of dissolved substances and, importantly, CO2‐philicity. In this Review, the theoretical work that has been relevant to these developments is surveyed and, by presenting some crucial open questions, the possible routes to achieving further progress based on the interplay between theory and experiments is discussed.