Cytokines represent a heterogeneous group of soluble mediators which are involved in almost any physiological and pathological process. The release of many cytokines and numerous of their biological activities are mediated by nuclear factor-kappaB (NF-kappaB). NF-kappaB is a ubiquitous transcription factor which is crucially involved in many biological processes, including tissue development and maintenance of tissue homeostasis. NF-kappaB also controls apoptotic cell death of both normal and malignant cells. Thus, it is a challenging target for anticancer and anti-inflammatory strategies. However, it has been recognized that NF-kappaB does not only influence many biological processes but also under certain conditions the activities of NF-kappaB can be altered as well, for example, by cytokines. This cross talk needs to be taken into account when developing strategies targeting NF-kappaB for anticancer therapy.