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Nuclear Factor-kappaB (NF-κB) has been implicated in the lobuloalveolar development of the mammary gland. In breast cancer its activation has been linked to tumor progression via stimulation of cell proliferation, pro-survival, and angiogenesis pathways and metastasis. Whether NF-κB activation in the immune system influences mammary cancer remains unclear. In addition to the constitutive activation frequently found in mammary carcinoma tissue, radio- and chemotherapeutic agents used in the treatment of mammary cancer can lead to activation of NF-κB. This effect has been postulated to contribute to the development of resistance to these agents and suggests the use of NF-κB inhibitors as sensitizers for therapy. The review describes principle targets and drugs used to inhibit NF-κB function and discusses future perspectives in the use of these inhibitors for the treatment of mammary cancer.