The Rel/NFkappaB family of transcription factors is involved in multiple cellular processes, including inflammation, cell cycle regulation, apoptosis and oncogenesis. Constitutive activation of NFkappaB has been described in a great number of solid tumors and this activation appears to support cancer cell survival and to reduce the sensitivity against chemotherapeutic drugs. Additionally, some of these drugs induce this transcription factor themselves and through this mechanism lower their cytotoxic potential. Inhibition of NFkappaB by various means has been shown to enhance the sensitivity to antineoplastic- or radiation-induced apoptosis in vitro and in vivo. Furthermore, suppression of NFkappaB results in attenuation of cancer cachexia and metastasis in some mouse tumor models. Studies are underway to further delineate the role of NFkappaB in cancer cell survival, growth and resistance to standard chemotherapy and radiation regimens. Moreover, the effects of novel therapeutic agents which specifically target NFkappaB proteins are currently being assessed in experimental models of cancer cell growth both in vitro and in vivo. In this review, we discuss the possible involvement of NFkappaB in the chemoresistance of various solid tumors and potential future treatment strategies based on NFkappaB inhibition.