Nuclear transcription factor κB (NF-κB) was first discovered in 1986 in the nucleus of the B cell as an enhancer in the κ immunoglobulin chain. However, this factor has identified in the cytoplasm in the resting state. When activated in response to inflammatory stimuli, carcinogens, stress, ionizing radiation, and growth factors; NF-κB translocates to the nucleus where it upregulates the expression of over 400 different gene products linked with inflammation, cell survival, proliferation, invasion, and angiogenesis. The activation of NF- κB has now been linked with a variety of inflammatory diseases, including cancer and pulmonary, autoimmune, skin, neurodegenerative, and cardiovascular disorders. Indeed, constitutive NF-κB activation frequently correlates with the proliferation, survival, chemoresistance, radioresistance, and progression of various cancers. Hence, NF-κB has both diagnostic and prognostic applications. In addition, pharmaceutical companies are aggressively pursuing development of inhibitors of NF-κB with therapeutic potential. Thus within last decades this transcription factor, discovered serendipitously, has moved from “clone to clinic”.