Weeds are recognized globally as a major constraint to crop production and food security. In recent decades, that constraint has been minimized through the extensive use of herbicides in conjunction with genetically modified resistant crops. However, as is becoming evident, such a stratagem is resulting in evolutionary selection for widespread herbicide resistance and the need for a reformation of current practices regarding weed management. Whereas such a need is recognized within the traditional auspices of weed science, it is also imperative to include emerging evidence that rising levels of carbon dioxide (CO<sub>2</sub>) and climatic shifts will impose additional selection pressures that will, in turn, affect herbicide efficacy. The goal of the current perspective is to provide historical context of herbicide use, outline the biological basis for CO<sub>2</sub>/climate impacts on weed biology, and address the need to integrate this information to provide a long-term sustainable paradigm for weed management.
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