In many parts of the world, major regional drinking water resources are represented by large-scale sandstone aquifers. In particular in arid climate zones, society depends on the water from such aquifer systems because of the lack of alternative renewable drinking water resources. The often fossil (and hence non-renewable) groundwaters of deep sandstone aquifer systems are not likely to show any anthropogenic contamination. However, sandstone tends to contain elevated concentrations of naturally occurring radionuclides, which has potential impact on the water quality with regard to the groundwater use, giving rise to health related issues. The activity concentration of a certain radionuclide in groundwater depends on (1) the occurrence of the radionuclide or its parent nuclides in the aquifer matrix, (2) the intensity of element mobilization from the mineral grains and (3) the potential ways of natural element removal from the groundwater. As a result, the overall radionuclide concentration in groundwater is determined by the mineralogical composition of the aquifer matrix and by the existing geochemical/hydrochemical conditions, which might change with time as a result of groundwater mining (e.g. due to overexploitation). If elevated radionuclide concentrations in a groundwater sample have to be suspected, an undifferentiated analysis and assessment of all potentially present radionuclides is not appropriate. Whereas some radionuclide species represent a disproportionately high risk and have to be taken into account, most radionuclides do not have to be considered from a radio-ecological point of view. That is due to the poor solubility of some elements, due to the very short half-lives of many of the radionuclides and due to very low natural concentrations of many radionuclide species. Hence, designing a smart approach for the assessment and handling of elevated radionuclide activities in groundwater is compulsory. Such an approach must consider smart ways of (1) localizing and assessing the contamination, (2) careful groundwater mining, (3) state-of-the-art water treatment and (4) after-treatment NORM disposal. Especially the smart treatment of waters containing radionuclides is crucial to maximize the usable fraction of the resources. Typical removal of radionuclides employs ion exchange, reverse osmosis, as well as precipitation with hydroxides, carbonates, or sulphides. However, selective sorbents specifically tailored for radionuclide removal might represent a cost effective alternative to these well established techniques.