The management of soft tissue sarcomas has been highlighted in the last few years by the responsiveness of gastrointestinal stromal tumors to imatinib (Gleevec, Novartis). In this article, the use of chemotherapeutic agents in the management of this and some of the 50 or more subtypes of sarcomas are discussed, and a brief review of the use of chemotherapy in the adjuvant or neoadjuvant setting for people with large extremity sarcomas is provided. Doxorubicin and ifosfamide (Mitoxana, Bristol-Myers Squibb) remain the best individual drugs for sarcomas overall, although dacarbazine and gemcitabine (Gemzar, Eli Lilly) with or without a taxane has activity in at least a subset of sarcomas. The data regarding adjuvant chemotherapy for extremity soft tissue sarcomas is still quite mixed, with little if any overall survival advantage found to support its incorporation into disease management. The finding of tyrosine kinase inhibitors such as imatinib with demonstrated activity in gastrointestinal stromal tumors and dermatofibrosarcoma protuberans, as well as the finding of new agents such as ecteinascidin-743 (Yondelis, PharmaMar) with at least some activity against soft tissue sarcomas, reinforces the idea that we should target individual subtypes of sarcoma, just as treatment varies by subtype for the hematological malignancies.