The purposes of this study are to determine:

1. The safety of Pemetrexed plus Gemcitabine and any side effects that might be associated with the combination of these two drugs.
2. Whether Pemetrexed plus Gemcitabine can help patients with mesothelioma live longer.
3. Whether Pemetrexed plus Gemcitabine can make the tumor smaller or disappear, and for how long.
4. To see if patients feel better while taking Pemetrexed plus Gemcitabine.

Inclusion Criteria:

• Diagnosis of mesothelioma that can be treated with chemotherapy
• Have received no prior chemotherapy for mesothelioma
• Have at least one measurable lesion
• Have an adequate performance status
• Sign an informed consent

Exclusion Criteria:

• Previous treatment with chemotherapy for mesothelioma
• Treatment with an investigational drug within the last 30 days, previously completed or withdrawn from this study or any other study investigating Pemetrexed
• Treatment with radiation therapy within the last 4 weeks
• Brain metastasis that is uncontrolled
• Active infection or other serious condition