- Plant secondary metabolites (natural products) have been a source for many of our medicines. Their functions in plants remain often unknown, but in recent years there are more and more new compounds isolated and identified and their medicinal potential investigated. The major classes of plant natural products and various derivatives thereof are: phenolics, terpenoids, alkaloids and lignans. The major transcription factor, nuclear factor-κB (NF-κB) is a central downstream regulator of inflammation, cell proliferation and apoptosis that controls the expression of more than 500 genes. It plays an essential role in several aspects of human health including the development of innate and adaptive immunity. The deregulation of NF-κB is associated with many ailments including cancer and chronic inflammatory diseases. In spite of a vast literature describing NF-κB inhibitors from many natural or synthetic sources, such modulators have not been fully tapped for therapeutic purposes and the search for effective and specific inhibitors for therapeutic use and minimal side effects is still relevant and ongoing. Plant-derived phytochemicals are promising lead compounds to develop potent and safe inhibitors for cancer and inflammatory disorders driven by NF-κB. We briefly review the recent knowledge on plant derived phytochemicals and their major NF-κB molecular targets.