All of our cells have the same genome sequence. The topic of this chapter is understanding how that shared and constant genome sequence acts differently in different cell types, responds to the environment, and changes throughout our lives. Chemical modifications to the genome sequence and to the proteins that package the genome, known collectively as the epigenome, are a major contributor to the changes in genome function between cell types and over time. This chapter will describe the basic components of the epigenome; how the epigenome is established and maintained; the role of the epigenome in health and disease; and current and future directions in epigenetic and epigenomic research.