Malignant pleural mesothelioma is an aggressive malignancy which is almost always fatal; median survival is usually < 1 year. Most patients present with symptoms including pain, dyspnoea, pleural effusions and chest wall masses. Until recently, there has been no effective treatment which can improve symptoms and prolong survival. This article reviews recent developments in the treatment of mesothelioma, particularly advances in drug therapy and the use of the current most active drug combination: pemetrexed and cisplatin. Pemetrexed is a novel antifolate drug with multiple enzyme targets. The combination of pemetrexed and cisplatin demonstrated a survival advantage over cisplatin alone in patients with pleural mesothelioma, and can give symptomatic benefits. This combination has become the standard of care in mesothelioma treatment.