Trabectedin (Yondelis); ET-743) is an antineoplastic agent that was originally derived from the Caribbean marine tunicate Ecteinascidia turbinata and is now produced synthetically. It binds to the minor groove of DNA, disrupting the cell cycle and inhibiting cell proliferation. Intravenous trabectedin administered once every 3 weeks is approved as monotherapy in Europe for use in patients with advanced soft tissue sarcoma (STS) after failure of standard therapy with anthracyclines or ifosfamide, or who are unsuited to receive these agents. It also has orphan drug status in STS in the US and in ovarian cancer in the US and Europe, and is under investigation as combination therapy in patients with recurrent ovarian cancer. In clinical trials, trabectedin showed efficacy in the treatment of patients with advanced or metastatic STS, especially those with leiomyosarcoma or liposarcoma, as well as in women with platinum-sensitive advanced or recurrent ovarian cancer. In addition, its tolerability profile was generally manageable. The introduction of trabectedin expands the currently limited range of effective treatment options for patients with advanced or metastatic STS; trabectedin also has the potential to be a beneficial treatment for advanced or recurrent ovarian cancer.