Nonpoint source pollution is the runoff of pollutants (including soil and nutrients) from agricultural, urban, and other lands (as opposed to point source pollution, which comes directly from one outlet). Many efforts have been made to combat both types of pollution, so why are we making so little progress in improving water quality by reducing runoff of soil and nutrients into lakes and rivers? This essay examines the challenges inherent in: 1) producing science to predict and assess nonpoint management and policy effectiveness; and 2) using science for management and policy-making. Barriers to demonstrating causality include few experimental designs, different spatial scales for behaviors and measured outcomes, and lags between when policies are enacted and when their effects are seen. Primary obstacles to using science as evidence in nonpoint policy include disagreements about values and preferences, disputes over validity of assumptions, and institutional barriers to reconciling the supply and demand for science. We will illustrate some of these challenges and present possible solutions using examples from the Yahara Watershed in Wisconsin. Overcoming the barriers to nonpoint-pollution prevention may require policy-makers to gain a better understanding of existing scientific knowledge and act to protect public values in the face of remaining scientific uncertainty.