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Meat is an integral part of the diet of many people. The consumption of meat has tremendously contributed to human evolution, and its huge variability within and between populations reflects economic development. It is a valuable source of energy and essential nutrients. Nevertheless, over the last decades a considerable number of epidemiological studies have reported positive associations between high red meat and especially processed meat consumption and all-cause mortality and the risk to develop colorectal cancer, cardiovascular disease and diabetes, whereas these associations are not present with white meat (poultry) consumption. The largest body of evidence is available for colorectal cancer. It should be mentioned that the increases in relative risk of chronic diseases with high red meat and/or processed meat consumption are rather low, and that more mechanistic studies are needed to prove causality. Compounds and processes that may be involved in the negative effects of meat consumption on human health can be divided in compounds intrinsic to meat (e.g. heme-Fe) and compounds formed during processing or preparation of meat prior to consumption (e.g. heterocyclic amines, polycyclic aromatic hydrocarbons), or in the gastrointestinal tract during digestion (e.g. trimethylamine-N-oxide), or both prior to or during gastrointestinal digestion (e.g. N-nitroso-compounds, oxidation products). The nature, formation and potential role of the compounds most considered at present are discussed in this chapter, as well as possible mitigation strategies. Very likely, there is no single causal factor responsible for each of the associations due to the interaction of meat with other foods and with the microbiome in the gastrointestinal tract. It is therefore advocated that dietary patterns rather than foods should be investigated when considering nutritional prevention of chronic diseases. Meats consumed as part of balanced diets with preference for unprocessed and minimally processed meats and in line with nutritional guidelines do not pose a health risk.