Bipolar disease (BPD) is a complex major psychiatric disorder that affects between 1% and 2% of the population and exhibits ?85% heritability. This has made BPD an appealing target for genetic studies yet, despite numerous attempts, the genetic basis of this disease remains elusive. Recently, it has come to light that epigenetic factors may also influence the development of BPD. These factors act via stable but reversible modifications of DNA and chromatin structure. In this chapter, we revisit the epidemiological, clinical, and molecular findings in BPD and reanalyze them from the perspective of inherited and acquired epigenetic misregulation. Epigenetic research has great potential to enhance our understanding of the molecular basis of BPD.