Geogenic groundwater contaminants (GGCs) affect drinking-water availability and safety, with up to 60% of groundwater sources in some regions contaminated by more than recommended concentrations. As a result, an estimated 300–500 million people are at risk of severe health impacts and premature mortality. In this Review, we discuss the sources, occurrences and cycling of arsenic, fluoride, selenium and uranium, which are GGCs with widespread distribution and/or high toxicity. The global distribution of GGCs is controlled by basin geology and tectonics, with GGC enrichment in both orogenic systems and cratonic basement rocks. This regional distribution is broadly influenced by climate, geomorphology and hydrogeochemical evolution along groundwater flow paths. GGC distribution is locally heterogeneous and affected by in situ lithology, groundwater flow and water–rock interactions. Local biogeochemical cycling also determines GGC concentrations, as arsenic, selenium and uranium mobilizations are strongly redox-dependent. Increasing groundwater extraction and land-use changes are likely to modify GGC distribution and extent, potentially exacerbating human exposure to GGCs, but the net impact of these activities is unknown. Integration of science, policy, community involvement programmes and technological interventions is needed to manage GGC-enriched groundwater and ensure equitable access to clean water.