As climate change has impacted water resources globally, drinking water resources are particularly at risk. The nature of the risk may differ when there is an overabundance of water through flooding or when droughts and rising temperatures lead to insufficient water resources, or when the surface and groundwater sources are polluted. In each case, there is a clear burden of disease. The estimates of the burden of disease may be direct, in the form of morbidity and mortality rates associated with gastrointestinal or respiratory infections and diseases, or indirect, in the form of lost employment or educational opportunities, each with varying economic impacts. The economic analyses involve accounting for the costs of providing clean drinking water and minimizing contamination of water supplies, as well as the benefits of access and availability of safe and clean drinking water. Global-scale climate and environmental degradation often lead to migration, loss of agricultural production and income, poverty, gender disparity, and other challenges that indirectly impact access to clean drinking water. Economists and health researchers are now having to contend with these variables that previously remained separated from scientific and technical models. A systems approach that shows the interlinkages between these variables can serve as a valuable tool to expand the current economic models used in estimates of the burden of disease and other methodologies used to assign value to drinking water.