Mid-sized lakes exemplify several key challenges for sustainable freshwater management during the next century. Increasing population will heighten both drinking water demands and pressure on wastewater treatment, both in terms of emerging micropollutants and with respect to treatment capacity. Expected increases in average temperature and changing precipitation patterns linked to climate change may alter physical, chemical and biological dynamics of the lake and could thus affect future water quality in ways that are still unknown. Increasing recreational use of the lake, changes in catchment land use, the use of thermal energy from the lake and other developments will also impact water quality. The ecosystem and human inhabitants will bear the consequences of these increasing pressures on the lake. Key needed insights into the physical, chemical, microbiological, and ecological dynamics of mid-sized lakes would enable us to anticipate and manage properly these risks.