Zinc is an essential nutrient that is required for a broad range of biological functions. The potential exists for zinc to impact on chronic disease. The aims of this chapter are twofold: firstly to evaluate the epidemiological and clinical data that report on zinc status and atherosclerosis in humans, and secondly to determine the potential mechanisms of the interaction of zinc with atherosclerosis risk factors. There are conflicting reports of the relationship between atherosclerosis and zinc status, as assessed by dietary intake of zinc and/or the measurement of zinc concentrations in healthy and diseased tissues. The balance of epidemiological studies points to an association between zinc deficiency and atherosclerosis however the studies are hampered by the lack of a decisive biomarker of zinc status. Clinical trials are mainly of zinc supplementation, and these show a decrease in plasma high-density lipoprotein cholesterol concentrations leading to an increased risk of heart disease. Impaired zinc homeostasis has been associated with increased levels of oxidative stress and the induction of widespread genomic and proteomic changes that relate to cardiovascular disease. Potential mechanisms of the influence of zinc on atherogenesis studied in rodent models and in cell culture include its interaction with a wide range of cellular redox and inflammatory processes, such as NF-kB, NO, PPAR, and PKC signalling pathways. In conclusion, zinc is likely to be involved in atherogenesis through its interactions with lipoprotein metabolism, inflammation and oxidative stress. Further progress will be made when improved methods of measuring zinc status are developed.