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Cancer is a multistep process during which cells acquire genetic alterations that drive the progressive transformation of normal cells into highly malignant cells. Self-sufficiency in growth, insensitivity to anti-growth signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, tissue invasion and metastasis, are signatures of transformed cells. NF-kappaB is a key actor in tumorigenesis given its ability to control the expression and the function of a number of genes involved in these processes. Indeed, constitutive activation of NF-kappaB is a common feature of many human tumors, while its sustained activation during inflammation predisposes normal cells to neoplastic transformation. Since suppression of NF-kappaB has been shown to inhibit oncogenic potential of transformed cells, targeting it should be effective in the prevention and treatment of cancer.