Upstream-downstream problems are a class of problems in which activities occurring “upstream” are removed from their effects, which are felt “downstream.” A defining characteristic of these problems is that benefits and costs are asymmetrically distributed. Rivers are the archetypal setting in which these problems occur. This paper explores the case of the Kuskokwim River in Alaska where the utilization of natural resources has created a series of dynamic and interconnected upstream-downstream problems. Increased commercial salmon harvests, primarily in the lower river, have impacted subsistence fisheries. Record high salmon catches and salmon prices in 1988 allowed fishermen to capitalize boats and gear, facilitating their ability to travel upriver to hunt moose. These changes reconfigured upstream-downstream relationships, altered the fit of institutions to natural systems, led to new types of resource conflicts, created institutional challenges, and provide insights into institutional design.