The Konza Prairie LTER Program (KNZ) is a comprehensive, interdisciplinary research program designed to provide a mechanistic and predictive understanding of ecological processes in mesic grasslands, and contribute to synthesis and conceptual advances in ecology. Konza LTER also offers education and training at all levels (K-12 to postgraduate) as well as public outreach, and contributes ecological knowledge essential for addressing land-use and management issues in grasslands. Our focal research site is the Konza Prairie Biological Station, 3487 ha of native tallgrass prairie in the Flint Hills of NE Kansas. With LTER funding, we have amassed long-term datasets (many that span >25 yrs) on key ecological processes such as hydrology, nutrient cycling, productivity, and community and population dynamics of plants and consumers. These long-term records provide unique insights into the dynamics and functioning of tallgrass prairie ecosystems, while serving as a critical baseline for identifying and interpreting ecological responses to environmental change in mesic grasslands globally. The KNZ program encompasses diverse studies that span multiple ecological levels and a range of spatial and temporal scales. The unifying conceptual framework guiding this body of research is that three key drivers – fire, grazing and climatic variability – are essential and interactive factors shaping the origin, evolution, persistence and functioning of tallgrass prairie, with relevance to grasslands globally. The interplay of these drivers across a heterogeneous landscape leads to high species diversity and complex ecological dynamics, making KNZ data relevant for addressing many basic ecological issues (e.g., productivity-diversity relationships, disturbance and community stability, top-down vs. bottom-up controls, the interplay of mutualistic and antagonistic biotic interactions, and biotic responses to present and future environmental variability). Because human activities directly (managing grazers and fire) and indirectly (changing atmospheric chemistry and climate) alter the key drivers of ecological processes in grasslands worldwide, KNZ research is increasingly used to address critical global change issues, including land-use and land-cover change, altered biogeochemistry and hydrology, and climate change. Current research themes were chosen to foster integration across disciplines, biological levels of organization, and temporal and spatial scales of study: (1) Land-use and land-cover change, including (a) impacts of changing fire-grazing regimes (b) causes/consequences of woody plant expansion, and (c) ecosystem restoration; (2) Ecological responses to climatic variability and climate change; (3) Responses to altered biogeochemical cycles; (4) Aquatic ecology and effects of altered water quality and hydrology; and (5) Regionalization, remote sensing, and modeling.