(1) Fisheries science in the 21st century requires an ecosystem approach to management that considers ecological sustainability and sets clear goals measured by multiple indicators of ecosystem, species, and human well-being. (2) An ecosystem approach involves monitoring environmental and species indicators over time, assessing fisheries resource status, and providing forecasts to evaluate how changing practices may impact the ecosystem. (3) Key themes of an ecosystem approach include considering the entire system, setting ecological boundaries, ensuring sustainability, using adaptive management, and recognizing humans as part of nature.