Treatment of persistent gestational trophoblastic neoplasia (GTN) has been one of the success stories of modern day chemotherapy; however, occasional patients with metastatic disease still die. A potential difficulty in assessing published studies is that patient groups can be selected for treatment differently according to how risk categories are defined. The involvement of a specialist team from the outset is essential. Patients with low-risk metastatic GTN are treated successfully with single-agent chemotherapy using methotrexate or dactinomycin. Patients with high-risk metastatic disease receive combination chemotherapy regimens from the start. Worldwide experience has been accrued by use of regimens devised and tested by large centres. The high response rate and good long-term survival, as well as the tolerable acute and cumulative toxic effects, associated with use of etoposide, methotrexate and dactinomycin, alternating with cyclophosphamide and vincristine, make this protocol, or one of its variants, the current initial treatment of choice for patients. In view of the success of these regimens difficulty would be encountered in mounting a worthwhile randomised controlled trial; however, further well-designed studies are needed of novel approaches in very-high-risk and multiresistant disease.