Transcriptionally active DNA is packaged with histones that are post-translationally acetylated on multiple lysines within their amino termini.  While the majority of this acetylation is limited to the promoters of genes, acetylated histones are also found throughout transcribed units.  Over the last decade we have uncovered many of the pathways involved in directing histone acetylation to active genes.   This review will summarize much of this groundbreaking research as well as discuss some of the outcomes of this important protein post-translational modification.