Etoposide (VP-16-213) is an antineoplastic agent with demonstrated efficacy against a broad spectrum of human malignancies, including testicular, germ cell, lung, and other cancers. Etoposide can be synergistic with other agents. As part of combination chemotherapy, etoposide has become a so-called standard in therapies for testicular cancer and small cell lung cancer. Its activity in tumors such as lymphoma and leukemia, as well as solid tumors, identifies etoposide as a highly important chemotherapeutic agent. Cellular and animal models have shown that the cell kill and tumor response depend on both dose and time of exposure. Recent clinical studies again show that dose and schedule of etoposide can have important effects on clinical response to the drug. Further research should now continue: (1) on the use of etoposide as part of initial therapy in several cancers, and (2) in higher doses and prolonged schedules to optimize this agent's potential.