This paper presents an overview of the global extent of naturally occurring toxic metals in groundwater. Adverse health effects attributed to the toxic metals most commonly found in groundwater are reviewed, as well as chemical, biochemical, and physiological interactions between these metals. Synergistic and antagonistic effects that have been reported between the toxic metals found in groundwater and the dietary trace elements are highlighted, and common behavioural, cultural, and dietary practices that are likely to significantly modify health risks due to use of metal-contaminated groundwater are reviewed. Methods for analytical testing of samples containing multiple metals are discussed, with special attention to analytical interferences between metals and reagents. An overview is presented of approaches to providing safe water when groundwater contains multiple metallic toxins.