The transcription factor nuclear factor–κB (NF-κB) 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-κB 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-κB activity as humans and animals age, with tissue-specific increases and decreases in NF-κB activity being reported. The extent to which changes in NF-κB activity drive aging and influence life span in humans and other mammals is not clear. However, given the dramatic impact that NF-κB can have on the function of numerous tissues and organs, understanding how NF-κB activity changes with age will undoubtedly enhance our understanding of the many diseases associated with growing old.