Histone post-translational modifications (PTMs) have a crucial role in chromatin regulation and dynamics. They are specifically bound by so called reading domains, which mediate the biological effects of histone PTMs. On the same note, antibodies are invaluable reagents in chromatin biology for the detection, characterization and mapping of histone PTMs. Despite these central roles in chromatin research and biology, the specificity of many antibodies and reading domains is insufficiently characterized and documented. In this book chapter we describe in detail the application of the MODified™ Histone Peptide Array for the investigation of the binding specificity of histone binding antibodies or domains. The array contains 384 histone tail peptides carrying 59 post translational modifications in different combinations which apart from studying the primary binding specificity can also allow to determine the combinatorial effect of secondary marks on antibody or reading domain binding.