The Mid-Atlantic region hosts some of the most mature karst landscapes in North America, developed in highly deformed rocks within the Piedmont and Valley and Ridge physiographic provinces. This guide describes a three-day excursion to examine karst development in various carbonate rocks by following Interstate 70 west from Baltimore across the eastern Piedmont, across the Frederick Valley, and into the Great Valley proper. The localities were chosen in order to examine the structural and lithological controls on karst feature development in marble, limestone, and dolostone rocks with an eye toward the implications for ancient landscape evolution, as well as for modern subsidence hazards. A number of caves will be visited, including two commercial caverns that reveal strikingly different histories of speleogenesis. Links between karst landscape development, hydrologic dynamics, and water resource sustainability will also be emphasized through visits to locally important springs. Recent work on quantitative dye tracing, spring water geochemistry, and groundwater modeling reveal the interaction between shallow and deep circulation of groundwater that has given rise to the modern karst landscape. Geologic and karst feature mapping conducted with the benefit of lidar data help reveal the strong bedrock structural controls on karst feature development, and illustrate the utility of geologic maps for assessment of sinkhole susceptibility.