Atherosclerosis, the major cause of death and disability in the United States, is a chronic disease with inflammatory components. The first objective of this review is to explain how activation of NF-kappa B contributes to atherosclerosis. The second objective is to describe a potential link between inflammation, activation of NF-kappa B, and periodontitis. The nuclear transcription factor NF-kappa B controls the expression of many genes linked to atherogenesis including those involved with inflammation. We hypothesize that one unifying mechanism in this complex disease is the activation of NF-kappa B. The mechanism(s) that activates NF-kappa B in atherogenesis is unknown and the effect of inhibiting NF-kappa B activation on atherogenesis is untested. Periodontal disease has now been established as a risk factor for atherosclerosis and its thrombotic complications. It is unknown if periodontal disease contributes to the initiation or progression of atherosclerosis. We hypothesize that the chronic and intense inflammatory response accompanying periodontal disease produces an excess burden of circulating mediators of inflammation that initiate or exacerbate the inflammatory components of atherogenesis. Further understanding of the mechanisms involved in the activation of NF-kappa B in atherosclerosis could lead to important therapeutic applications especially as it relates to the impact of periodontitis.