Rapid increases in herbicide resistance have highlighted the ability of weeds to undergo genetic change within a short period of time. That change, in turn, has resulted in an increasing emphasis in weed science on the evolutionary ecology and potential adaptation of weeds to herbicide selection. Here we argue that a similar emphasis would also be invaluable for understanding another challenge that will profoundly alter weed biology: the rapid rise in atmospheric carbon dioxide (CO2) and the associated changes in climate. Our review of the literature suggests that elevated CO2 and climate change will impose strong selection pressures on weeds and that weeds will often have the capacity to respond with rapid adaptive evolution. Based on current data, climate change and rising CO2 levels are likely to alter the evolution of agronomic and invasive weeds, with consequences for distribution, community composition, and herbicide efficacy. In addition, we identify four key areas that represent clear knowledge gaps in weed evolution: (1) differential herbicide resistance in response to a rapidly changing CO2/climate confluence; (2) shifts in the efficacy of biological constraints (e.g., pathogens) and resultant selection shifts in affected weed species; (3) climate-induced phenological shifts in weed distribution, demography, and fitness relative to crop systems; and (4) understanding and characterization of epigenetics and the differential expression of phenotypic plasticity versus evolutionary adaptation. These consequences, in turn, should be of fundamental interest to the weed science community.