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Knowledge of epigenetic alterations in disease is rapidly increasing owing to the development of genome-wide techniques for their identification. The ever-growing number of genes that show epigenetic alterations in disease emphasizes the crucial role of these epigenetic alterations - particularly DNA methylation - for future diagnosis, prognosis and prediction of response to therapies. This Review focuses on epigenetic profiling, which has started to be of clinical value in cancer and may in the future be extended to other diseases, such as neurological and autoimmune disorders.