In eukaryotic cells, the genome is packaged with histones H2A, H2B, H3, and H4 to form nucleosomes. Each of the histone proteins is extensively post-translationally modified, particularly in the flexible N-terminal histone tail domains. Curiously, while post-translational modifications in histone H3 and H4 have been extensively studied, relatively little is known about post-translational modifications in the N-terminal domains of histone H2A and H2B. In this review, we will summarize current knowledge of post-translational modifications in the N-terminal domains of histone H2A and H2B, and the histone variant H2AZ. We will examine the distribution of these modifications in genomic chromatin, and the function of these modifications in transcription.