We compared the effects of water resource development on migratory fish in two North American rivers using a descriptive approach based on four high-level indicators: (1) trends in abundance of Pacific salmon, (2) reliance on artificial production to maintain fisheries, (3) proportion of adult salmon that are wild- versus hatchery-origin, and (4) number of salmon populations needing federal protection to avoid extinction. The two rivers had similar biological and physical features but radically different levels of water resource development: the Fraser River has few dams and all are located in tributaries, whereas the Columbia River has more than 130 large mainstem and tributary dams. Not surprisingly, we found substantial effects of development on salmon in the Columbia River. We related the results to potential effects on migratory fish in the Mekong River where nearly 200 mainstem and tributary dams are installed, under construction, or planned and could have profound effects on its 135 migratory fish species. Impacts will vary with dam location due to differential fish production within the basin, with overall effects likely being greatest from 11 proposed mainstem dams. Minimizing impacts will require decades to design specialized fish passage facilities, dam operations, and artificial production, and is complicated by the Mekong's high diversity and productivity. Prompt action is needed by governments and fisheries managers to plan Mekong water resource development wisely to prevent impacts to the world's most productive inland fisheries, and food security and employment opportunities for millions of people in the region.