Premise: The tallgrass prairie ecosystem has experienced a dramatic reduction over the last 150 years. This reduction has impacted the abundance of native grassland species including milkweeds (Asclepias). Methods: Here we use two long-term (27-year) datasets to examine how fire, grazing, and nutrient addition shape milkweed abundance in tallgrass prairie. We compare these results to a greenhouse experiment that varies nutrient levels in the absence competition, herbivory, and mutualistic relationships. Key Results: We find that Asclepias species exhibit broad patterns in response to burning regimes that do not include grazing, but experience more species-specific patterns in other combinations. Asclepias syriaca was the only species to increase in abundance in plots that included burning and nutrient addition. In the greenhouse we find that nitrogen significantly increases biomass while no effect of phosphorus was detected. Conclusions: These results indicate that A. syriaca will do best in settings with high nutrient loads, low competition, and no grazers. These characteristics define a small portion of the tallgrass prairie, while these conditions exemplify modern agricultural settings, which have replaced prairies. However, other milkweed examined did not share this pattern. This indicates that milkweed species will respond differently when exposed to agricultural settings, with some less able to cope with land conversion to pasture or row crop agriculture.