Nuclear factor-B (NF-B) is a major transcription factor that plays an essential role in several aspects of human health including the development of innate and adaptive immunity. The dysregulation of NF-B is associated with many disease states such as AIDS, atherosclerosis, asthma, arthritis, cancer, diabetes, inflammatory bowel disease, muscular dystrophy, stroke, and viral infections. Recent evidence also suggests that the dysfunction of NF-B is a major mediator of some human genetic disorders. Appropriate regulation and control of NF-B activity, which can be achieved by gene modification or pharmacological strategies, would provide a potential approach for the management of NF-B related human diseases. This review summarizes the current knowledge of the physiological and pathophysiological functions of NF-B and its possible role as a target of therapeutic intervention