MicroRNAs (miRNAs) are small non-coding RNAs that bind to the 3'untranslated region of target mRNAs and lead to translation repression or mRNA degradation, thus regulating important cell processes. MiRNA deregulation has been identified in virtually all types of cancer, and miRNA profiling has proved useful in cancer diagnosis, prognosis and response to therapy. So far, limited but important evidence of miRNA impaired expression has been reported in multiple myeloma (MM), suggesting implications in the pathogenesis and biology of the disease. In this review, we present a general overview of the role of miRNAs in B-cell development and associated malignancies, focusing on those most extensively characterized. We fully describe seminal studies on miRNA expression in MM, highlighting the correlations of their deregulation with pathogenesis and with distinct molecular subgroups, as well as their role in prognostic stratification. The data obtained in MM, supported by the consolidated role of miRNAs in cancer and their potential effectiveness in therapy, all provide a solid rationale for the more accurate characterization of their deregulation and the development of effective means of selectively delivering miRNAs and anti-miRNAs to myeloma cells in therapeutic approaches.