The sustainability of water resources is under continued threat from the challenges associated with a growing population, competing demands, and a changing climate. Freshwater scarcity has become a fact in many areas. Much of the United States surface-water supplies are fully apportioned for use; thus, in some areas the only potential alternative freshwater source that can provide needed quantities is groundwater. Although frequently overlooked, groundwater serves as the principal reserve of freshwater in the US and represents much of the potential supply during periods of drought. Some nations have requirements to monitor and characterize the availability of groundwater such as the European Union’s Water Framework Directive (EPCEU 2000). In the US there is no such national requirement. Quantitative regional groundwater availability assessments, however, are essential to document the status and trends of groundwater availability for the US and make informed water-resource decisions possible now and in the future. Barthel (2014) highlighted that the value of regional groundwater assessments goes well beyond just quantifying the resource so that it can be better managed. The tools and techniques required to evaluate these unique regional systems advance the science of hydrogeology and provide enhanced methods that can benefit local-scale groundwater investigations. In addition, a significant, yet under-utilized benefit is the digital spatial and temporal data sets routinely generated as part of these studies. Even though there is no legal or regulatory requirement for regional groundwater assessments in the US, there is a logical basis for their implementation. The purpose of this essay is to articulate the rationale for and reaffirm the value of regional groundwater assessments primarily in the US; however, the arguments hold for all nations. The importance of the data sets and the methods and model development that occur as part of these assessments is stressed. These high-value data sets and models should be available in readily accessible formats for use today and in the future. Examples of advances in and accomplishments of two regional groundwater assessments are presented to demonstrate their function, relevance, and value for determining the sustainability of the groundwater resources of the US.