Pemetrexed disodium (ALIMTA, LY231514 (MTA)) is a novel multitargeted antifolate, that inhibits at least three enzymes involved in folate metabolism and DNA synthesis. These enzymes are thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase. This agent has shown broad antitumor activity in phase II trials in a wide variety of solid tumors, including non-small cell lung cancer, breast, colon, pancreas, bladder, head and neck, and cervical carcinomas, and is undergoing randomized phase III studies. MTA has also shown promising activity in a broad range of tumors in combination with other active agents such as gemcitabine and cisplatin. The clinical pharmacology, toxicity and clinical activity of MTA are reviewed in this report.