Weed management is a critically important activity on both agricultural and non-agricultural lands, but it is faced with a daunting set of challenges: environmental damage caused by control practices, weed resistance to herbicides, accelerated rates of weed dispersal through global trade, and greater weed impacts due to changes in climate and land use. Broad-scale use of new approaches is needed if weed management is to be successful in the coming era. We examine three approaches likely to prove useful for addressing current and future challenges from weeds: diversifying weed management strategies with multiple complementary tactics, developing crop genotypes for enhanced weed suppression, and tailoring management strategies to better accommodate variability in weed spatial distributions. In all three cases, proof-of-concept has long been demonstrated and considerable scientific innovations have been made, but uptake by farmers and land managers has been extremely limited. Impediments to employing these and other ecologically based approaches include inadequate or inappropriate government policy instruments, a lack of market mechanisms, and a paucity of social infrastructure with which to influence learning, decision-making, and actions by farmers and land managers. We offer examples of how these impediments are being addressed in different parts of the world, but note that there is no clear formula for determining which sets of policies, market mechanisms, and educational activities will be effective in various locations. Implementing new approaches for weed management will require multidisciplinary teams comprised of scientists, engineers, economists, sociologists, educators, farmers, land managers, industry personnel, policy makers, and others willing to focus on weeds within whole farming systems and land management units.