Fresh waters are central to society and to the environment. Nevertheless, ongoing and projected changes in the distribution, abundance, and quality of water resources and freshwater ecosystems represent a serious threat to the integrity of the environment as well as the vitality of human cultures. Nearly every country in the world experiences regular water shortages, agriculture uses most of the world's available fresh water, and most illnesses in developing countries result from waterborne parasites and pathogens. Unfortunately, often hidden in these and other depressing statistics are the needs of the environment for adequate water to maintain vibrant ecosystems. Understanding the abilities and limits of freshwater ecosystems to respond to human-generated pressures is becoming a central issue for cultures and a challenge for science. This article explores trends in alterations to freshwater ecosystems, discusses the ecological consequences of biophysical alterations expected to occur in the next 20–30 years, and identifies some of the major scientific challenges and opportunities to effectively address the changes. Topics discussed include altered hydrological regimes, biogeochemical cycles, altered land use, riparian management, life history strategies, and relations between climate change and water resource management.