The inflammatory response is of major importance in host defence, but is 
involved in all acute and chronic diseases. Multiple inflammatory cells and 
molecules are involved. Among the latter, the Nuclear Factor -κB (NF-κB) has 
been found to be most important and present in all cell types. NF-B regulates 
the expression of a large number of genes involved in inflammation. NF-κB plays 
a key role in the orchestration of the multifaceted inflammatory response, not 
only in the first pro-inflammatory phase, but also later in the regulation of 
the resolution of inflammation, when anti-inflammatory genes are expressed and 
apoptosis is induced. The review describes NF-κB and its two pathways: the 
canonical, mediated by the p65 and p50 subunits, and the non-canonical, mediated 
by the subunits RelB, p52 and p50. The relevance of the kinases and interactions 
leading to NF-κB activation is considered in different primary cells (i.e. 
macrophages, dendritic cells, fibroblasts, cells from inflammatory tissues), 
together with the response induced and the ligand involved. Then we overview the 
different steps to NF-B activation that can be targeted (IKKs, IκBα or NF-κB 
subunits themselves) with various technologies available i.e. small molecules 
peptides or nucleic acids. A rationale is provided for possible targets to 
consider, in the light that NF-κB signaling pathways regulates both 
pro-inflammatory and anti-inflammatory responses. The possibility of using NF-κB 
targeted dendritic cells in immunotherapy is considered.