In South Africa, mining and industrial activity may cause toxic substances including metals to pollute surface and groundwater resources. Furthermore, there is an increased public awareness regarding pesticides, fertilisers, agricultural products and metals that might endanger our indigenous fish populations and aquatic ecosystems. This is mainly because humans use these natural resources as food and water supplies and are therefore also exposed to products polluting these resources. Of particular concern is the exposure of bio-organisms to metal pollution, as it is known that metals act as mutagenic/genotoxic compounds, interfere with xenobiotic metabolic pathways, and may also affect glycolysis, the Krebs cycle, oxidative phosphorylation, protein amino acid metabolism as well as carbohydrate and lipid metabolism. Therefore, in this review, we discuss the two phases of the central metabolic pathways, as well as how metals affect the different enzymes and metabolic processes in these pathways. The focus is particularly on metals most frequently found in groundwater in South Africa and include cadmium (Cd), copper (Cu), aluminium (Al), zinc (Zn), lead (Pb), arsenic (As), iron (Fe), manganese (Mn) and chromium (Cr). We conclude that metals in the environment and polluting our groundwater may have a major impact on human and animal life and that ultimately exposure to these products may be the cause of many diseases due to their effect on the central metabolic pathways.