Pathogenesis-related (PR) responses are closely integrated with primary metabolism and influenced by simple compounds involved in plant nutrition, such as sugars, organic acids, and amino acids. Photorespiratory metabolism linked to enhanced production of reactive oxygen species (ROS) in peroxisomes can induce typical PR responses. Growing plants at increased CO₂ levels, which slows photorespiratory rates, can also induce defense metabolism and PR genes, effects that are accompanied by upregulation of ROS signaling. Genes involved in CO₂ sensing and signaling in stomatal regulation are beginning to be elucidated but components that link CO₂ availability to biotic stress responses remain to be identified. Emerging evidence suggests that metabolite and ROS signaling are likely to be important in linking CO₂ availability to the activation of defense metabolism.