Background/Question/Methods Inducible defenses allow organisms to minimize the fitness costs of defense in the face of variable herbivore pressure. In the work presented here, we explore the effects of changes in atmospheric CO2 concentrations on the inducibility of chemical defenses by Asclepias syriaca, the common milkweed. Furthermore, we examine induction by and the performance of two herbivore species: Danaus plexippus (monarch caterpillar) and Aphis asclepiadis on five different A. syriaca families. A. syriaca is common to the Eastern United States and is prey to many specialist insect herbivores. A. syriaca produces many putative and potentially inducible defenses, including cardenolides, latex, trichomes, and tough leaves. We germinated 80 individuals each of five full-sibling families of Asclepias syriaca originating from Northern Michigan. In a split plot design, replicate plants from each family were grown in the presence of two treatments: ambient and elevated CO2 concentrations (380 and 760 ppm, respectively). Caterpillars or aphids were caged on half of all 3 month-old plants for 5 or 9 days, respectively. Plants were harvested, their defensive and growth traits assessed, and caterpillars collected for growth measurements. Data were analyzed in R using linear models with chamber as a random effect. Results/Conclusions We found that although atmospheric CO2 concentrations significantly affected the constitutive production of defenses by Asclepias seedlings, CO2 did not affect the chemical induction response to herbivory by either caterpillars or aphids. Herbivory significantly affected plant regrowth and bud production on the root, measures of subsequent year growth and reproduction. Elevated CO2 did, however, mitigate the negative effects of herbivory on plant regrowth. Asclepias families varied in the production of foliar cardenolides and the extent of induction of the major cardenolide compound to herbivory. The performance of caterpillars was dependent on the interaction between CO2 and host plant family identity. We conclude that significant family-level variation in defensive phenotype exists and interactions with CO2 concentration affect herbivore performance through a combination of traits or some unmeasured trait. The broad-scale heritability in response to herbivory and herbivore performance on different plant families suggests that natural selection by insect herbivores in combination with elevated CO2 could result in changes in defense levels in Asclepias populations over time. Future atmospheric conditions will alter plant defensive traits and herbivore performance, but seem to more strongly affect growth rather than defense induction in A. syriaca seedlings.