Epigenetic mechanisms play a crucial role in the normal development of the mammalian organism and are essential for maintaining the cell identity and normal functionality. Global changes in the epigenetic landscape associated with aberrant gene expression are a hallmark of cancer. Current knowledge indicates that both epigenetic alterations and genetic aberrations play an important role in the onset and progression of cancer. Recent findings have demonstrated that in cancer extensive reprogramming of all components of the epigenetic machinery (including DNA methylation, histone modifications and miRNA expression) takes place and have furthermore revealed the existence of a dynamic interplay between the different components. However, the exact sequence of events and underlying molecular mechanism contributing to carcinogenesis are only just beginning to be uncovered. Interestingly, the reversal of aberrant epigenetic modifications has emerged as a potential treatment strategy of cancer. Here, we describe the role of the epigenetic alterations in the pathogenesis of cancer focusing on the hematological malignancy multiple myeloma. In addition, recent advances regarding the relationship between histone modifications, chromatin-modifying enzymes, DNA methylation and miRNA expression are discussed.