Lysine acetylation has been shown to occur in many protein targets, including core histones, about 40 transcription factors and over 30 other proteins. This modification is reversible in vivo, with its specificity and level being largely controlled by signal-dependent association of substrates with acetyltransferases and deacetylases. Like other covalent modifications, lysine acetylation exerts its effects through "loss-of-function" and "gain-of-function" mechanisms. Among the latter, lysine acetylation generates specific docking sites for bromodomain proteins. For example, bromodomains of Gcn5, PCAF, TAF1 and CBP are able to recognize acetyllysine residues in histones, HIV Tat, p53, c-Myb or MyoD. In addition to the acetyllysine moiety, the flanking sequences also contribute to efficient recognition. The relationship between acetyllysine and bromodomains is reminiscent of the specific recognition of phosphorylated residues by phospho-specific binding modules such as SH2 domains and 14-3-3 proteins. Therefore, lysine acetylation forges a novel signaling partnership with bromodomains to govern the temporal and spatial regulation of protein functions in vivo.