Our understanding of malignant mesothelioma has increased rapidly in the last 5 years. The prognosis remains poor for most patients, however. Radical surgery is inappropriate for most, and palliative chemotherapy can be toxic if used without care. Patient selection is crucial, and prognostic factors allow us to predict which patients are likely to benefit from intensive treatment. Longer survival is associated with epithelioid histology, earlier stage, female gender, left-sided primary, nonexposure to asbestos, no history of smoking, and a lack of symptoms at presentation. Numerous genes of significance are identified and many have been shown to correlate with clinical outcome. Molecular data will provide prognostication of exceptional accuracy, biologic insights, and targets for improved treatment.