Herbicide-resistant genetically-modified (GM) crops are the most widely cultivated worldwide, representing 78% of GM crops in 1999, followed by insect-resistant GM crops with Bt gene. Gene flow is the most touching risk arising from GM crops, and is categorized as three types: within species, between species and between GM crop and other organisms. This review shows that gene flow is a reality in the plant kingdom with evolutionary change. Herbicide resistance evolves naturally and spreads dynamically in weeds. One of the most concerning crop in relation to gene flow is Brassica napus, which has a high outcrossing rate and many relative species. In contrast, frequency of gene flow via outcrossing is relatively low in inbreeding cereal crops such as rice, wheat and barley, but published reports have shown that substantial gene flow is possible. Another possible and immediate risk is herbicide-resistant GM crops becoming volunteer weeds. Dry direct-seeded rice is one of the most likely crops in this respect. Stacking different resistance genes in a crop would accelerate multiple resistance evolution in weeds. Multiple resistance to three major herbicides has already been observed in oilseed rape cultivation. More efforts must be made for long-term risk assessment on GM crops in the natural ecosystem. More studies on weed biology and ecology, particularly reproductive processes in weeds, are essential for better understanding of gene flow and systematic management strategy. We hope that this review motivates researchers to analyze data available now, to collect fundamental information on crops and weeds in agro-ecosystem, and to lead to better risk assessment and management.