The “chromodomain” (Chromatin Organization Modifier) was originally described as a structural motif found in Drosophila proteins with gene-silencing functions (Polycomb and Heterochromatin Protein 1 (HP1)). The human proteome comprises 55 chromodomain-containing proteins, including Polycomb (Cbx’s 2, 4, 6-8) and HP1 (HP1 α, ß, γ) homologs. A key function of many chromodomains is the recognition and binding (‘reading’) of methylated lysine residues in histones and other proteins. For example the HP1 proteins, which function in the establishment and maintenance of heterochromatin, bind histone H3K9me2/3 residues, whereas the double-chromodomain protein CHD1 selectively binds H3K4me3 and Cbx7 binds H3K27me3. A number of chromodomain proteins (e.g. Cbx7, CHD4) are potential therapeutic targets for cancer.