Owing to the development of new technologies, the epigenome, a second dimensional method for genome analysis has emerged. Epigenetic mechanisms, including DNA methylation, histone modifications and noncoding RNAs, regulate gene expression without changing the genetic sequence. These epigenetic mechanisms normally modulate gene expression, trans-generational effects and inherited expression states in various biological processes. Abnormal epigenetic patterns typically cause pathological conditions, including cancers, age-related diseases, and specific cartilage and bone diseases. Facing the rapidly developing epigenetic field, we reviewed epigenetic mechanisms and their involvement with the skeletal system and their role in skeletal development, homeostasis and degeneration. Finally, we discuss the prospects for the future of epigenetics.