Most nuclear factor-kappaB (NF-kappaB) inducers converge to activate the IkappaB kinase (IKK) complex, leading to NF-kappaB nuclear accumulation. However, depending on the inducer and the cell line, the subset of NF-kappaB-induced genes is different, underlining a complex regulation network. Recent findings have begun to delineate that histone and non-histone protein acetylation is involved, directly and indirectly, in controlling the duration, strength and specificity of the NF-kappaB-activating signaling pathway at multiple levels. Acetylation and deacetylation events, in combination with other post-translational protein modifications, generate an 'NF-kappaB-signaling code' and regulate NF-kappaB-dependent gene transcription in an inducer- and promoter-dependent manner. Indeed, the intricate involvement of histone acetyltransferases and histone deacetylases modulates both the NF-kappaB-signaling pathway and the transcriptional transactivation of NF-kappaB-dependent genes.