Most published work on post-translational histone modifications focuses on small covalent alterations such as acetylation, methylation and phosphorylation. By contrast, fewer data are available on the modification of histones by ADP-ribose. Discussion of the biological significance of histone ADP-ribosylation has often been restricted to functions of the modifying enzymes, rather than to histones as ADP-ribose acceptors. In particular, the identification of specific lysine residues as ADP-ribose acceptor sites in histones and the identification of ADP-ribose binding modules raise this modification to a par with acetylation, methylation or phosphorylation. We discuss here the functional aspects of histone ADP-ribosylation and its influence on DNA repair, replication and transcription.