DNA methylation is one of the heritable epigenetic modifications, leading to repressed gene expressions and consequent phenotypic alterations without changing the DNA sequence. MicroRNA (miRNA) is a novel class of short non-coding RNA molecules regulating a wide range of cellular functions through translational repression of their target genes. Recently, epigenetic dysregulation of tumor-suppressor miRNA genes by promoter DNA methylation has been implicated in human cancers, including multiple myeloma (MM). This article presents a brief overview of the pathogenesis of MM, the role of DNA methylation in cancer biology, methods of DNA methylation analysis, miRNA biology and dysregulation of miRNAs in MM and summaries the current data on the role of DNA methylation of tumor-suppressive miRNAs in MM.