Freshwater ecosystems, including lakes, streams, and wetlands, are responsive to climate change and other natural and anthropogenic stresses. These ecosystems are frequently hydrologically and ecologically connected with one another and their surrounding landscapes, thereby integrating changes throughout their watersheds. The responses of any given freshwater ecosystem to climate change depend on the magnitude of climate forcing, interactions with other anthropogenic and natural changes, and the characteristics of the ecosystem itself. Therefore, the magnitude and manner in which freshwater ecosystems respond to climate change are difficult to predict a priori. We present a conceptual model to elucidate how freshwater ecosystems are altered by climate change. We identify eleven indicators that describe the response of freshwater ecosystems to climate change, discuss their potential value and limitations, and describe supporting measurements. Indicators are organized in three interrelated categories: hydrologic, water quality, and ecosystem structure and function. The indicators are supported by data sets with a wide range of temporal and spatial coverage, and they inform important scientific and management needs. Together, these indicators improve the understanding and management of the effects of climate change on freshwater ecosystems.