Historically, malignant pleural mesothelioma patients with potentially resectable disease have been treated with surgery and radiation alone. With improvements in systemic and intrapleural treatment options, a movement toward multi-modality therapy has become more common. Systemic treatment options largely consist of neoadjuvant chemotherapy with platinum doublets and most recently novel targeted agents, such as dasatinib. Intrapleural strategies have included injecting chemotherapy, chemotherapy with hyper thermic per fusion, gene therapy, and immunotherapy. The following review discusses the latest results in neoadjuvant and intrapleural therapies in malignant pleural mesothelioma.