Post-translational modifications (PTMs) of histones play a key role in DNA-based processes and contribute to cell differentiation and gene function by adding an extra layer of regulation. Variations in histone sequences within each family of histones expands the chromatin repertoire and provide further mechanisms for regulation and signaling. While variants are known to be present in certain genomic loci and carry out important functions, much remains unknown about variant-specific PTMs and their role in regulating chromatin. This ambiguity is in part due to the limited technologies and appropriate reagents to identify and quantitate variant-specific PTMs. Nonetheless, histone variants are an integral portion of the chromatin system and the understanding of their modifications and resolving how PTMs function differently on specific variants is paramount to the advancement of the field. Here we review the current knowledge on post-translational modifications specific to histone variants, with an emphasis on well-characterized PTMs of known function. While not every possible PTM is addressed, we present key variant-specific PTMs and what is known about their function and mechanisms in convenient reference tables.