Epigenetics is emerging as one of the most dynamic and vibrant biomedical areas. Multiple lines of evidence confirm that inherited genetic changes alone cannot fully explain all phenotypic characteristics of live organisms, and additional factors, which are not encoded in the DNA sequence, are involved. The contribution of non-genetic factors is perhaps best illustrated by monozygotic twins, which, despite sharing nearly identical DNA sequences, are often discordant for diseases they develop. Even when twins develop the same condition, they may experience different clinical manifestations or clinical onset at different ages. Epigenetic mechanisms explain how a zygote can differentiate into greater than 220 different cell types that form an adult organism and, with rare exceptions, share the same DNA. Increasingly, epigenetic factors emerge, in addition to genetic ones, as important contributors to carcinogenesis. Epigenetic modifications also explain the biological impact of environmental factors, including chemical and dietary compounds, physical agents, pathogens linked to cancer, and social-emotional interactions. Unlike genetic changes, epigenetic changes are reversible, a characteristic that opens unprecedented therapeutic avenues, exemplified by the first epigenetic drugs that were recently approved. Understanding the combined contribution of genetic and epigenetic factors to gene expression will be essential to dissect the biological networks shaping development and disease, and to develop a new array of prophylactic, diagnostic, and therapeutic applications.