The NF-${kappa}B$ pathway transcriptionally controls a large set of target genes that play important roles in cell survival, inflammation, and immune responses. While many studies showed anti-tumorigenic and pro-survival role of NF-${kappa}B$ in cancer cells, recent findings postulate that NF-${kappa}B$ participates in a senescence-associated cytokine response, thereby suggesting a tumor restraining role of NF-${kappa}B$. In this review, we discuss implications of the NF-${kappa}B$ signaling pathway in cancer. Particularly, we emphasize the connection of NF-${kappa}B$ with cellular senescence as a response to chemotherapy, and furthermore, present examples how distinct oncogenic network contexts surrounding NF-${kappa}B$ produce fundamentally different treatment outcomes in aggressive B-cell lymphomas as an example.