Some plant species are particularly well adapted to environments disturbed by humans. Often such species are invasive and problematic, and thus are classified as weeds. Despite our best efforts to manage weeds, they continue to interfere with crop production. There is clearly much to learn about weeds, information that could aid in weed management and improve competitiveness in nonweedy species. The tools of molecular biology have been enlisted in ongoing efforts to manage weeds, most notably in the development and commercialization of crop plants tailored to resist certain herbicides. Molecular biology also has been used to gain a better understanding of how weeds compete and interact with neighboring plants, survive harsh environmental conditions, and evolve resistance to the herbicides used to control them. The next generation of molecular biology tools, such as genomic resources, may yield novel weed management strategies and shed new light on what makes plants weedy.