Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a crucial transcription factor that participates in a number of physiological and pathological conditions, including immune response, apoptosis, carcinogenesis and inflammatory processes. It is involved in the rapid response to various stimuli such as viral and bacterial infections, shear stress, oxidant stress and a number of cytokines. In the pathology of atherosclerosis NF-κB is essential to the cross-talk between cytokines, adhesion molecules and growth factors, leading to atherosclerotic plaque formation, growth and eventual rupture. The intent of this paper is to gather and summarize information on the role of NF-κB in the pathology of atherosclerosis. Additionally, pharmacological intervention in the signaling of NF-κB is addressed along with the potential benefits and disadvantages of NF-κB modulating treatment.