The National Ecological Observatory Network (NEON) is a large facility project funded by the National Science Foundation. NEON is designed to collect and ultimately provide 30 years of data and information to scientists, educators, decision makers, and the general public to enable understanding and forecasting of the impacts of climate change, land use change, and invasive species on continental-scale ecology. To this end, NEON is collecting data in four ecological areas: (1) The Aquatic Program will collect data on ecological responses to physical and chemical drivers in freshwater systems; (2) The Airborne Observation Platform will observe land use change, plant canopies, and habitat structure characteristics in the region around NEON sites, using remote sensing instruments deployed on a light aircraft; (3) The Terrestrial Instrumental Measurements program observes climate (temperature, incoming radiation and outgoing radiation, humidity, wind velocity, precipitation) and climate-related physical variables in the plant canopy and soils; and (4) The Terrestrial Biological Measurements Program measures key response variables (diversity, genomics, disease prevalence, chemistry) in selected taxa (plants, insects, birds, small mammals, pathogens, microbes) and media (soil and water). NEON’s cyber infrastructure will therefore have to ingest billions of measurements per year from the 20 NEON domains, verify the quality of those measurements against predefined parameters, and provide the data via the internet to the research and education communities. Moreover, biological sampling efforts will require significant resources from natural history collections to provide (1) taxonomic expertise for species-specific identification, particularly for the invertebrates, (2) provide tissue samples to build a DNA barcode library to stream-line specimen identification over the long-term at NEON sites and beyond, and, (3) physical and informatics infrastructure to house specimens, tissue samples, and associated data. We hope that, in addition to meeting the project’s goals, our efforts will significantly contribute data, resources, and innovations to existing collections. We invite participation and feedback from the scientific community to help NEON succeed in this unprecedented continental-scale effort.