The molecular mechanisms for NF-kappaB signaling transduction and transcription have been the most attractive subjects for both basic research and pharmaceutical industries due to its important roles in both physiological and pathogenesis, particularly the close association of dysregulated NF-kappaB with tumorgenesis and inflammation. Several novel intracellular molecular events that regulate NF-kappaB activity have been described recently, including the discovery of an alternative signaling pathway that appears inducing a specific subset genes involved in adoptive immune response. Multi-level and multi-dimensional regulation of NF-kappaB activity by phosphorylation and acetylation modifications have unveiled and became the hottest targets for potentially tissue specific molecular interventions. Another emerging mechanism for NF-kappaB-responsive gene's regulation where NF-kappaB participates the transcriptional regulation independent of its cognate regulatory binding site within the target gene's promoter but facilitating the transaction activity of other involved transcription factors, that implicated an novel transcriptional activities for NF-kappaB. Thus, the current review will focus on these recent progresses that have been made on NF-kappaB signaling transduction and transcription.