Alterations to the natural flow regime affect the structure and function of rivers and wetlands and contribute to loss of biodiversity worldwide. Although the effects of flow regulation have been relatively well studied, a lack of synthesis of the ecological consequences of low flows and droughts impedes research progress and our grasp of the mechanistic effects of human-induced water reductions on riverine ecosystems. We identified 6 ecologically relevant hydrological attributes of low flow (antecedent conditions, duration, magnitude, timing and seasonality, rate of change, and frequency) that act within the temporal hierarchy of the flow regime and a spatial context. We synthesized the literature to propose 4 principles that outline the mechanistic links between these low-flow attributes and the processes and patterns within riverine ecosystems. First, low flows control the extent of physical aquatic habitat, thereby affecting the composition of biota, trophic structure, and carrying capacity. Second, low flows mediate changes in habitat conditions and water quality, which in turn, drive patterns of distribution and recruitment of biota. Third, low flows affect sources and exchange of material and energy in riverine ecosystems, thereby affecting ecosystem production and biotic composition. Last, low flows restrict connectivity and diversity of habitat, thereby increasing the importance of refugia and driving multiscale patterns in biotic diversity. These principles do not operate in isolation, and many of the ecological pathways that are affected by low flows are likely to overlap or occur simultaneously, potentially resulting in synergistic and complex effects. Last, we outlined major human-induced threats to low-flow hydrology and how they act upon the ecologically relevant hydrological attributes of low flow to affect potential changes in riverine ecosystem integrity. The mechanistic links described in this synthesis can be used to develop and test hypotheses of low-flow hydrological–ecological response relationships in a cause–effect framework that will have value for both research and river flow management. Continued experimental research and ongoing consolidation of ecological information will improve our understanding and ability to predict consequences of low-flow alteration on river, floodplain, and estuarine ecosystems.