Cardiovascular diseases are the leading cause of morbidity and mortality in Western countries. Atherosclerosis, the background for many cardiovascular diseases, is characterized by the accumulation of lipid and fibrotic entities in large arteries and bears many similarities with chronic inflammatory diseases such as rheumatoid arthritis. Common features include extravasation of blood-derived leukocytes, as well as production of cytokines, chemokines and matrix-degrading enzymes. There are also many shared signaling pathways, including activation of the nuclear factor κB (NFκB) cascade. In the context of atherosclerosis, there are a range of candidate stimuli which can activate NFκB, including traditional risk factors, infectious agents, cytokines and cell–cell contact. Many inflammatory genes relevant to the pathogenesis of atherosclerosis are regulated by NFκB, the activated form of which is present in atherosclerotic plaques. Thus, it is essential to understand the role of this important signaling cascade in atherosclerosis, in a quest for more specific therapeutic targets.