Recent studies suggest that the mammalian genome alone cannot completely explain many physiological and pathophysiological phenomena including variability in phenotypes, drug responses, discordance between monozygotic twins for the same trait or disorder, and disease susceptibility of an individual. The missing link could be epigenetic modifications of genome such as DNA methylation, numerous posttranslational modifications of histone proteins and regulation of expression of microRNAs. Epigenetic modifications are well known and are involved in normal mammalian development. They are modulated globally and in a gene-specific manner by environmental factors including nutrition, hormones, toxins, and drugs. Age also plays an important role in gene–environmental interactions. Epigenomic pathways are essential for normal cellular functions with abnormalities in their programming leading to complex disorders including psychiatric diseases. Epigenetic factors can thus serve as molecular markers to predict the responsiveness of diseases to therapy. Further knowledge of epigenomic changes and identification of factors that mediate alterations in the epigenome may lead to new drug targets and therapies. In this overview the importance of epigenomics in drug development and therapies has been highlighted.