The opportunity to target weed seeds during grain harvest was established many decades ago following the introduction of mechanical harvesting and the recognition of high weed-seed retention levels at crop maturity; however, this opportunity remained largely neglected until more recently. The introduction and adoption of harvest weed seed control (HWSC) systems in Australia has been in response to widespread occurrence of herbicide-resistant weed populations. With diminishing herbicide resources and the need to maintain highly productive reduced tillage and stubble-retention practices, growers began to develop systems that targeted weed seeds during crop harvest. Research and development efforts over the past two decades have established the efficacy of HWSC systems in Australian cropping systems, where widespread adoption is now occurring. With similarly dramatic herbicide resistance issues now present across many of the world's cropping regions, it is timely for HWSC systems to be considered for inclusion in weed-management programs in these areas. This review describes HWSC systems and establishing the potential for this approach to weed control in several cropping regions. As observed in Australia, the inclusion of HWSC systems can reduce weed populations substantially reducing the potential for weed adaptation and resistance evolution.