In patients who have advanced soft tissue sarcoma that is no longer localized, systemic chemotherapy is the most reasonable option for treatment. The decision to treat or to use experimental or conventional agents should be based on the clinical assessment of anticipated net benefit in quality of life as well as the remote possibility of complete remission or even cure. Asymptomatic elderly patients with relatively stable disease might best be treated with watchful waiting; whereas younger excellent-performance-status patients should be offered the opportunity of participating in phase II or phase I studies of newer drugs and intensification regimens. Of the currently available single agents, only doxorubicin (or epirubicin) and ifosfamide show response rates greater than 20%; both show a definite dose-response relationship. Dacarbazine shows particular activity in uterine leiomyosarcomas. Combination chemotherapy regimens such as doxorubicin-ifosfamide show a higher response rate, but may be more toxic. New agents are needed. The current progress in our understanding of the molecular biology of sarcomas, and our expanded comprehension of the mechanism of action of cytotoxic drugs and the biology of drug resistance is cause for optimism.