Nuclear factor kappaB (NF-kappaB), a transcription factor, plays an important role in carcinogenesis as well as in the regulation of immune and inflammatory responses. NF-kappaB induces the expression of diverse target genes that promote cell proliferation, regulate apoptosis, facilitate angiogenesis and stimulate invasion and metastasis. Furthermore, many cancer cells show aberrant or constitutive NF-kappaB activation which mediates resistance to chemo- and radio-therapy. Therefore, the inhibition of NF-kappaB activation and its signaling pathway offers a potential cancer therapy strategy. In addition, recent studies have shown that NF-kappaB can also play a tumor suppressor role in certain settings. In this review, we focus on the role of NF-kappaB in carcinogenesis and the therapeutic potential of targeting NF-kappaB in cancer therapy.