By concentrating materials and increasing the speed with which rainfall is conveyed off of the landscape, nearly all forms of land use change lead to predictable shifts in the hydrologic, thermal, and chemical regimes of receiving waters that can lead to the local extirpation of sensitive aquatic biota. In Central Appalachian river networks, alkaline mine drainage (AlkMD) derived from mountaintop removal mining for coal (MTM) noticeably simplifies macroinvertebrate communities. In this dissertation, I have used this distinct chemical regime shift as a platform to move beyond current understanding of chemical pollution in river networks. In Chapter Two, I applied a new model, the Hierarchical Diversity Decision Framework (HiDDeF) to a macroinvertebrate dataset along a gradient of AlkMD. By using this new modeling tool, I showed that current AlkMD water quality standards allow one-quarter of regional macroinvertebrates to decline to half of their maximum abundances. In Chapter Three, I conducted a field study in the Mud River, WV to understand how AlkMD influences patterns in aquatic insect production. This work revealed roughly 3-fold declines in annual production of sensitive taxa throughout the year in reaches affected by AlkMD. These declines were more severe during summer base flow when pollutant concentrations were higher, thereby preventing sensitive organisms from completing their life cycles. Finally, in Chapter Four I described the idea of chemical fragmentation in river networks by performing a geospatial analysis of chemical pollution in Central Appalachia. In this work I showed that the ~30% of headwaters that remain after MTM intensification over the last four decades support ~10% of macroinvertebrates not found in mined reaches. Collectively my work moves beyond the simple tools used to understand the static, local consequences of chemical pollution in freshwater ecosystems.