During progression of an in situ to an invasive cancer, epithelial cells lose expression of proteins that promote cell–cell contact, and acquire mesenchymal markers, which promote cell migration and invasion. These events bear extensive similarities to the process of epithelial to mesenchymal transition (EMT), which has been recognized for several decades as critical feature of embryogenesis. The NF-κB family of transcription factors plays pivotal roles in both promoting and maintaining an invasive phenotype. After briefly describing the NF-κB family and its role in cancer, in this review we will first describe studies elucidating the functions of NF-κB in transcription of master regulator genes that repress an epithelial phenotype. In the second half, we discuss the roles of NF-κB in control of mesenchymal genes critical for promoting and maintaining an invasive phenotype. Overall, NF-κB is identified as a key target in prevention and in the treatment of invasive carcinomas. J. Cell. Biochem. 104: 733–744, 2008. © 2008 Wiley-Liss, Inc.