Today’s interdisciplinary scientific environment requires that working models of catchment-scale hydrological processes recognize the influences of landscape and hydrologic controls on biogeochemical cycling and organic matter (OM) flux through surface water and groundwater systems. Examples from karst terrains in the Southeastern U.S. highlight the importance of accounting for wide variations in recharge and residence time, vadose-zone anisotropy, surface water-groundwater interactions, episodicity and seasonality, and photic (e.g., photo-synthesis, photodegradation) versus aphotic (e.g., sorption, oxidation) processes. In areas with low normalized base-flows, sinking stream recharge and spring discharge can increase by orders of magnitude during storm events, resulting in the introduction and transport of particulate matter and bacteria. Furthermore, natural OM concentration and composition can have profound effects on metal toxicity, radionuclide transport, and disinfection by-product formation in aquatic habitats and public water supply sources. Yet, despite their reputation for flashiness, regional carbonate aquifers exist at base flow conditions most of the time, and are highly resilient to drought. This presentation addresses episodicity at low flow conditions, which may be more pronounced than at moderate to high flows due to reduced epikarstic inputs and diffuse recharge during the dry season, and low-flow groundwater residences times that are an order of magnitude greater than the norm. This suggests that the published values for normalized base flow may be biased towards high flow tracer tests due to the time commitment required for low flow tests. The objectives of this research were to investigate the seasonal dynamics of microbially-driven OM degradation in a surface-influenced groundwater system, and to identify patterns and biomarkers of carbon cycle processes useful for monitoring long-term hydroecological trends in Appalachian watersheds. However, lessons learned from this study can help other researchers develop more representative sampling strategies, regardless of their objectives and geologic settings.