Technical Abstract: The genetic bases of weedy and invasive traits and their evolution remain poorly understood, but genomic approaches offer tremendous promise for elucidating these important features of weed biology. However, the genomic tools and resources available for weeds are currently relatively meager compared to those for many crops. Because genomic methodologies are becoming increasingly accessible and less expensive, the time is ripe for weed scientists to incorporate these methods into their research programs. One example is next-generation sequencing technology, which enables the sequencing of an entire transcriptome of a weedy plant in a single experiment. Successful implementation of these approaches will require collaborative efforts that focus resources on common goals and bring together expertise in weed science, molecular biology, plant physiology, and bioinformatics. We outline how these large-scale genomic programs can aid both our understanding of the biology of weedy and invasive plants and our success at managing these species. The judicious selection of species for developing weed genomics programs is needed, and we offer up choices, but no Arabidopsis-like species exists in the world of weeds. We outline the roadmap for creating a powerful synergy of weed science and genomics, given well-placed effort and resources.