The Chesapeake Bay is the largest estuary in the United States, encompassed by a watershed extending 168,000 km2 over portions of six states and Washington, D.C. Restoration of the Bay has been the focus of a two-decade regional partnership of local, state and federal agencies, including a network of scientists, politicians and activists interacting through various committees, working groups, and advisory panels. The effectiveness of the restoration effort has been mixed, with both notable successes and failures. The overall health of the Bay has not declined since the restoration was initiated in 1983, but many of the advances have been offset by the pressure of increasing population and exurban sprawl across the watershed. The needs of the Chesapeake Bay Program are many, but the greatest is accurate information on land cover and land use change, primarily to assess the implications for water quality, examine various restoration scenarios, and calibrate spatial models of the urbanization process. We report here on a number of new land cover and land use data products, and associated applications to assist vulnerability assessment, integrated ecosystem analysis, and ultimately Bay restoration. We provide brief overviews of applications to model new residential development, assess losses and vulnerability of resource lands, and identify the factors that disrupt the health of streams in small watersheds. These data products and approaches are being applied by a number of agencies involved with the restoration effort, including the Chesapeake Bay Program’s activities focused on living resources, water quality, and sound land use.