Herbicide-resistant crops (HRCs), particularly glyphosate-resistant soybean, are increasingly important in Latin America. Prior to commercial release of these crops, their short- and long-term risks should be thoroughly assessed. A risk assessment should include the identification and characterization of potential hazards and an estimation of the likelihood of these hazards occurring. For HRCs the agro-ecological hazards are mostly related to the occurrence of herbicide-resistant (HR) weeds and crop volunteers and the adverse effects from the use of pesticides within the agricultural area. Herbicide-resistant rice is used as a case study to visualize the key components of such a risk assessment. For this purpose, a model that simulates a typical rain-fed rice production system in Central America was developed. The model was used to investigate the selection of HR weedy rice populations under various scenarios. Scenarios included contrasting weed management practices, hybridization levels between the commercial HR cultivated and weedy rice, and seed predation rates. Because risks may become apparent only after long-term cultivation of HR rice, simulations were run for a 10-yr period. In a cropping system relying on glufosinate-resistant rice for weed control, the model predicted that resistance to glufosinate would occur after 3 to 8 yr of monoculture. Increasing the hybridization level from 1 to 5% decreased the time for resistance to occur by 1 to 3 yr. Increasing annual rate of weedy rice seed predation at the soil surface delayed the development of resistance. Tillage as a weed control tactic also delayed the occurrence of resistance when compared with a no-till situation.