The transcription factor nuclear factor-kappa B (NF-kappaB) is involved in the regulation of a broad spectrum of genes that play important roles in a myriad of physiological and pathological events ranging from the immune response to carcinogenesis. Interestingly, many processes in which NF-kappa B plays a central role have long been noted for their alteration with age. A number of research groups have reported rather dramatic changes in NF-kappaB activity as humans and animals age, with tissue-specific increases and decreases in NF-kappaB activity being reported. The extent to which changes in NF-kappaB activity drive aging and influence life span in humans and other mammals is not clear. However, given the dramatic impact that NF-kappaB can have on the function of numerous tissues and organs, understanding how NF-kappaB activity changes with age will undoubtedly enhance our understanding of the many diseases associated with growing old.