A workshop was held in Baltimore, Maryland in January 2003 to discuss translational aspects of cancer therapies targeted at impacting aberrant gene transcription due to epigenetic changes. The mission of the meeting was the development of strategies for scientifically sound, clinically feasible applications targeting epigenetics in cancer therapy. Sessions included preclinical discussions of DNA methylation, the histone code, chromatin remodeling, and transcriptional control. Data on the histone deacetylase and DNA methyltransferase inhibitors under preclinical and clinical investigation were presented and discussed. The optimal correlative laboratory studies for monitoring clinical trials with these agents remain controversial. DNA methyltransferase and histone deacetylase inhibitors will be combined with each other to maximally re-express genes silenced through promoter methylation. Other classes of agents that may be rationally combined with these classes of drugs include retinoids, steroid hormones, and cytotoxic drugs.