Generalized and quantitative relationships between flow and ecology are pivotal to developing environmental flow standards based on socially acceptable ecological conditions. Informing management at regional scales requires compiling sufficient hydrologic and ecological sources of information, identifying information gaps, and creating a framework for hypothesis development and testing. We compiled studies of empirical and theoretical relationships between flow and ecology in the South Atlantic region (SAR) of the United States to evaluate their utility for the development of environmental flow standards. Using database searches, internet searches, and agency contacts, we gathered 186 sources of information that provided a qualitative or quantitative relationship between flow and ecology within states encompassing the SAR. A total of 109 of the 186 sources had sufficient information to support quantitative analyses. Ecological responses to natural changes in flow magnitude, frequency, and duration were highly variable regardless of the direction and magnitude of changes in flow. In contrast, the majority of ecological responses to anthropogenic-induced flow alterations were negative. Fish abundance, diversity, reproduction, and habitat consistently showed negative responses to anthropogenic flow alterations, whereas other ecological categories (e.g., macroinvertebrates and riparian vegetation) showed somewhat variable responses and even positive responses (e.g., algal abundance). Fish and organic matter had sufficient sample sizes to stratify natural flow-ecology relationships by specific flow categories (e.g., high flow, baseflows) or by physiographic province (e.g., Coastal Plain, Piedmont). After stratifying relationships, we found that significant correlations existed between changes in natural flow and fish responses. In addition, a regression tree explained 57% of the variation in fish responses to anthropogenic and natural changes in flow. Altogether, our results suggested that the source of flow change and the ecological category of interest played primary roles in determining the direction and magnitude of ecological responses. Furthermore, our results suggest that developing broadly generalized relationships between ecology and changes in flow at a regional scale is unlikely unless relationships are placed within meaningful contexts, such as environmental flow components or geomorphic settings.