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Double-strand breaks are one the most severe types of DNA damage with respect to cell survival and the preservation of genomic integrity. Therefore, cells have evolved complex mechanisms including cell cycle regulation, activation of repair pathways and in certain cases induction of apoptosis in response to these lesions. The molecular details of many of the cellular responses to double-strand breaks have been well characterized. Our understanding of these responses in the context of chromatin has also progressed recently. In this review, we focus our discussion on the significance of DNA damage-induced chromatin modifications in double-strand break signaling and repair pathways. In particular, findings from recent studies suggest mechanisms by which highly localized double-strand breaks may activate widespread signals throughout the cell by inducing alterations in chromatin structure.