Epigenetic therapy is highly anticipated as a next player to molecular target drugs. Epigenetic abnormalities are maintained even after a somatic cell division, and can be causally involved in carcinogenesis. Recent cancer genome analysis revealed that a significant fraction of cancers cannot be accounted for only by mutations of known protein-coding genes, and that mutations of epigenetic genes are unexpectedly frequent. DNA demethylating drugs and histone deacetylase inhibitors are already approved, and many next-generation epigenetic drugs are under development. Application of epigenetic therapies to solid tumors is being attempted, and a promising result is available for non-small cell lung cancers. Right patients, right doses, and right combinations are key to further success, and can be done based on recent progresses in mechanistic analyses.