The NF-kB-dependent signaling pathways are essential components of cellular response to stress. Mammalian family of NF-kB consists of five NF-kB/Rel proteins, which are subunits of the NF-kB transcription factor, and four IkB proteins, which are their specific inhibitors. Activation of NF-kB requires degradation of IkB, which allows nuclear translocation of NF-kB and its binding to cisacting DNA regulatory elements. NF-kB transcription factors regulate expression of numerous genes, which are involved in cell proliferation, apoptosis, immune response and inflammatory response. The NF-kB-dependent signaling pathways interfere with two other stress-related pathways regulated by p53 and HSF1 transcription factors. All three pathways are essential for both pathogenesis of serious human diseases, including cancer, and for response to therapeutic treatment.