Abstract: Modulation of chromatin is essential to nuclear processes that utilize DNA, such as transcription, replication, and repair. For example, transcription is assisted by histone post-translational modifications, as well as chromatin-remodeling complexes, which alter the structure of chromatin. Furthermore, recent advancements in the fields of DNA repair and chromatin reveal that both histone modifications and chromatin-remodeling complexes are essential for the repair of DNA lesions. In particular, chromatin-modifying complexes, such as the INO80 chromatin-remodeling complex and the Tip60 histone acetyltransferase complex, associate with the DNA damage-induced phosphorylated H2AX, which is often referred to as gamma-H2AX. In S. cerevisiae, the association of INO80 with gamma-H2AX is required for the recruitment of INO80 to sites of DNA double-strand breaks. Additionally, in Drosophila, Tip60 exchanges gamma-H2AX for unmodified H2A in regions of DNA damage. This report reviews recent studies that emphasize the intimate relationship between evolutionarily-conserved chromatin-modifying complexes and histone post-translational modifications in the repair of DNA damage.