The NF-kappaB (nuclear factor kappaB) family of transcription factors are involved in a myriad of activities, including the regulation of immune responses, maturation of immune cells, development of secondary lymphoid organs and osteoclastogenesis. Fine tuning by positive and negative regulators keeps the NF-kappaB signalling pathway in check. Microbial products and genetic alterations in NF-kappaB and other signalling pathway components can lead to deregulation of NF-kappaB signalling in several human diseases, including cancers and chronic inflammatory disorders. NF-kappaB-pathway-specific therapies are being actively investigated, and these hold promises as interventions of NF-kappaB-related ailments.