MicroRNAs are a class of small, non-coding RNAs that can function as tumor suppressors or oncogenes by regulating gene expression. This link was first reported in 2004, and has since been tied to a variety of malignancies, including malignant pleural mesothelioma (MPM). MPM is a malignancy arising in the mesothelial cells lining the lung pleura and is associated with chronic asbestos exposure. Despite the possibility for observing declining localized occurrence, global MPM is predicted to remain constant or increase slightly over the next decade. Global occurrence in combination with poor overall survival, difficulty in diagnosis, and limited effective treatment options signal the need for further exploration of miRNA involvement in MPM. Accordingly, this review highlights miRNA profiles associated with the diagnosis, prognosis, and therapeutic approaches in MPM.