The treatment of malignant mesothelioma (MM) has been challenging. Many series from larger single institutions comprise small numbers of selected patients. Positive studies tend to be published, whereas publication of negative studies is delayed, appears in obscure journals, or does not occur at all. Because of the pleural distribution of the tumor, reliable determination of response is problematic. Finally, the natural history of MM is generally short, but can be quite variable. Nevertheless, doxorubicin, cisplatin, and ifosfamide and perhaps other agents as well have modest activity. Larger phase II studies are now being done by cooperative groups accruing patients from community hospitals as well as from tertiary care centers. In the Cancer and Leukemia Group B study, the response rate in patients with measurable disease was 24% for cisplatin and either mitomycin C and doxorubicin, the highest response rates reported for a cooperative group study. Survival was slightly better for the doxorubicin combination. Studies of new drugs and biologics as well as of novel methods of drug delivery are underway.