The evolution of herbicide resistance in weed communities is a growing issue in the US Midsouth, Midwest, and across the world. Widespread herbicide resistance challenges the sustainability of our production systems and reactive strategies to manage resistant weeds constitute negative economic and environmental consequences. Some no-till growers have reverted to tillage to control resistant weeds, jeopardizing the soil conservations gains made in the past. Moreover, the discovery of new herbicide molecules has been stagnant and no new herbicide is expected to be available in the near future. Proactive strategies are crucial to sustainably manage weed communities and protect the existing herbicide options. A pioneering approach in this arena is the application of simulation models to understand the risk of resistance evolution and identify integrated management strategies that are more effective in preventing/managing resistance. The resistance simulation model includes three major components: ecology and biology, genetics, and management. Model parameterization requires a wide-array of knowledge and specific experiments encompassing inter-disciplinary tools and expertise to bridge knowledge gaps. Another equally important, but rather less understood area is the subsequent spread of resistance across a landscape through pollen and seed movement. The presentation will focus on some of the key expertise from the ongoing research in this area and how it will be used to address the emerging weed management issues of Indiana agronomic crop production systems.