Malignant Mesothelioma (MM) is an asbestos related malignancy with a poor prognosis and limited therapeutic approaches. The pathogenesis of MM has been linked to asbestos induced inflammation. Asbestos exposure results in reactive oxygen species generation, infiltration of inflammatory cells and prolonged release of multiple cytokines, oxidants and growth factors. The role of inflammation in MM has led to the evaluation of inflammatory profiles as prognostic and therapeutic markers. Additionally, inflammatory pathways are under investigation for potential therapeutic interventions. In this review, we discuss the role of inflammation in MM pathogenesis, inflammatory markers with potential clinical impact for MM and clinical trials that target inflammatory pathways and responses for treatment of MM. Ultimately, MM remains a difficult to treat cancer that requires multimodality therapy.