Revealing, and indeed exacerbating, the globe's present water crisis is the failing ecological health of rivers. Those who would protect and restore river health can learn important lessons from humanity's continual fight against disease. We discuss four of these lessons, including their applicability to river issues: (1) recognize and respond to changing challenges, (2) avoid unintended consequences, (3) employ both cure and prevention, and (4) take a systematic approach. The overarching message from human health science is that we need to view human actions and their consequences for river health in an integrated way. In an effort to construct such a view of river degradation, we suggest that human actions jeopardize river health in five major ways : (1) altering physical habitat, (2) modifying seasonal flow of water, (3) changing the food base of the system, (4) changing interactions within the river biota, and (5) polluting with chemical contaminants. Another key lesson of human health science is the need for a commonly understood and robust measure of river condition, or health. Biological monitoring and assessment using the index of biological integrity for Japanese streams (IBI-J) provides a rigorous measure of river condition as well as guidance on the causes of river degradation. Examples of the index's use in Japan illustrate the importance of various stressors responsible for degradation, such as amount and types of effluent, proximity of dams and other structural alterations, and riparian condition. They also show the dangers of management driven solely by narrow water quality measures such as biochemical oxygen demand (BOD). We conclude that biological measures are important because they provide a strong scientific framework to inform the largely cultural process of deciding how humans treat rivers.