It has long been suspected that NF-κB signaling has a pivotal role in chronic inflammation-associated malignancies, although genetic evidence for this hypothesis has been lacking. However, recent papers have lent credence to this concept and show that NF-κB activation in pre-malignant cells contributes to cell survival and metastatic potential. Furthermore, NF-κB activation in tumor-associated leukocytes, especially macrophages, contributes towards tumorigenesis by upregulating tumor-promoting proinflammatory proteins. This emphasizes the importance of NF-κB inhibitors as immunotherapeutic agents for chronic inflammation and suggests that these reagents might prevent, or at least inhibit, chronic inflammation-associated tumorigenesis.