In the last decade, etoposide has become a standard component of first-line combination chemotherapy in germ cell cancer. The replacement of vinblastine by etoposide in primary treatment came after the therapeutic efficacy of etoposide-containing regimens was determined to be equivalent or superior to vinblastine, with diminished short-term side effects. Subsequent investigations in the salvage setting have demonstrated that high-dose carboplatin and etoposide regimens coupled with autologous bone marrow transplantation can cure some patients with highly resistant disease, and that novel scheduling of etoposide using daily, oral, low-dose therapy can provide effective palliation in some patients. Although these therapeutic successes have been clouded by the demonstration of secondary acute leukemias in rare patients who have received high-dose etoposide, the challenge of the 1990s will be to capitalize on the clinical leads of dose and scheduling as well as to continue to document the long-term safety of these agents.