Recent years have seen major advances in elucidating the complexity of chromatin and its role as an epigenetic regulator of gene expression in eukaryotes. We now have a basic understanding of chromatin control and the enzymatic modifications that impart diverse regulatory cues to the functional activity of the genome. Most importantly, although research into chromatin has uncovered fascinating insights into the control of gene expression, it has also generated a large body of information that is being harnessed to develop new therapeutic modalities for treating cancer. Here, we discuss recent advances that support the contention that future generations of chromatin-modulating drugs will provide a significant group of new, mechanism-based therapeutics for cancer.