Nuclear factor-kappaB(NF-kB) is a group of pleiotropic transcription factors. NF-kB proteins play pivotal roles in immune and inflammatory responses. The pathophysiology of severe pneumonia involves complex cytokine and inflammatory mediator networks. NF-kB activation is a central molecular event leading to activation of these net-works and development of severe pneumonia. Importantly,blockade of NF- kB pathway corrects the pathological abnormalities and improves outcome of severe pneumonia. The critical role of NF-kB activation in severe pneumonia pathophysiology and the effectiveness of inhibiting NF-kB activation in correcting severe pneumonia abnormalities indicate that targeting NF-kB is a desired therapeutic strategy for treatment of severe pneumonia.