Nuclear factor-kappaB pathway plays important roles in the control of cell proliferation, differentiation, apoptosis, inflammation, stress response, cell signaling transduction, and other physiological processes. Because the disorder of these physiological processes has been linked with the onset of cancers, NF-kappaB has been described as a major culprit in cancer. Experimental in vitro and in vivo studies have shown that down-regulation of NF-kappaB activity by natural and synthetic NF-kappaB inhibitors suppresses the development of carcinogen-induced tumors, inhibits the growth of cancer cells, and induces apoptosis with alternation of gene expression which is critical for the control of carcinogenesis and cancer cell survival. Moreover, recent studies indicate that the effects of conventional cancer therapeutics could be enhanced by natural and synthetic NF-kappaB inhibitors, suggesting that down-regulation of NF-kappaB could sensitize cancer cells to conventional therapeutics. Therefore, targeting NF-kappaB is a novel preventive and therapeutic strategy against human cancers. In this brief review article, we will summarize the state of our knowledge for the role of NF-kappaB in relation to cancer prevention and therapy.