Nuclear transcription factor NF-kappaB, initially discovered as a factor in the nucleus of B cells that binds to the enhancer of the kappa light chain of immunoglobulin, has since been shown to be expressed ubiquitously in the cytoplasm of all cell types, conserved from Drosophila to man. It translocates to the nucleus only when activated, where it regulates the expression of over 200 genes that control the immune system, growth, and inflammation. The dysregulation of NF-kappaB can mediate a wide variety of diseases including cancer. Whether NF-kappaB activation is beneficial or harmful for cancer is controversial. The development of novel therapeutics targeting NF-kappaB requires full understanding of its role in pathology and physiology. The current review is an attempt to describe two sides of the NF-kappaB coin; viz, as a friend and as a foe.