Zinc has multiple roles in maintaining the physiological conditions of the cardiovasculature. Because atherosclerosis is a disease marked by chronic inflammation and oxidative stress, the antioxidant and anti-inflammatory properties of zinc are of obvious importance in the prevention of cardiovascular diseases. The anti-inflammatory properties of zinc are not well understood. Zinc is involved in multiple cell signaling pathways, implicated in the pathogenesis of atherosclerosis. The fact that inflammation itself affects zinc by changing intracellular zinc concentrations and distributions makes the role of zinc in inflammation even more complex. In addition, zinc protects the cardiovasculature from oxidative damage by preventing the formation of free radicals and the oxidation of macromolecules. Thiol groups of proteins, for example are protected from oxidation by zinc. Zinc chelated by thiol groups however, can be replaced by small reactive molecules during inflammation and oxidative stress. In certain cell signaling molecules this process appears to be the mechanism of activation/inactivation in response to inflammation. In addition, zinc also plays a crucial role in gene expression acting on the DNA, RNA and protein level. Zinc is required by transcription factors, RNA processing enzymes, as well as by protein folding chaperones. The response of cells and organisms to zinc supplementation or deprivation is therefore complex and further complicated during inflammatory processes such as atherosclerosis.