Epigenetic changes are important etiological factors of human tumor. The integrity of the genome is frequently challenged by the damage of DNA. However, the highly condensed structure of chromatin imposes significant obstacles on the repair processes. Eukaryotes have developed intricate mechanisms to overcome this repressive barrier imposed by chromatin. Covalent histone modifications and ATP-dependent chromatin remodeling play important roles in the process of DNA repair. Recent advances of the epigenetic regulations in the repair process were summarized. New findings in the cellular responses to DNA double strand breaks and how histone modifications and chromatin remodeling contributes to DNA double strand break repair were introduced. Future challenges in this field are also discussed.