Knowledge gaps concerning how various human activities combine to impact freshwater ecosystems can result in reported damaging “ecological surprises.” Although ecological surprises are typically linked to synergistic interactions between stressors, recent research highlights that the antagonistic effect by the single worst stressor most often defines a cumulative ecological impact. Here, use of the appropriate null model based on the known magnitude and mode of action of each stressor is essential to defining and managing cumulative impacts by multiple stressors. Our research shows that by using this approach one should focus on local stressors associated with human activities rather than regional stressors (e.g., climate warming) as the former often overshadows the effect of the latter.