Neoplastic transformation of mesothelium is commonly associated with exposure to asbestos and gives rise to malignant mesothelioma, an aggressive disease that has proved particularly refractory to conventional anti-cancer therapies. The Wnt signaling pathways play key roles in fundamental processes, which include both development and homeostasis. The importance of these pathways in tumorigenesis is emphasized by the many cancers which show aberrations in Wnt signaling. In this review we examine the current evidence for activation of Wnt signaling and the abnormal expression of specific molecules in malignant mesothelioma.