Trabectedin (Yondelis) is a tetrahydroisoquinoline molecule that was originally derived from a marine organism. It is indicated in the EU and many other countries for use in patients with advanced soft-tissue sarcoma (STS) who have progressed despite receiving previous treatment with anthracyclines and ifosfamide or in those who are unable to receive these agents. It is also approved in the EU in combination with pegylated liposomal doxorubicin for the treatment of platinum-sensitive, recurrent ovarian cancer. In addition, trabectedin holds orphan drug status for the treatment of advanced, recurrent STS in the US, Switzerland and Korea, and for the treatment of advanced, recurrent ovarian cancer in the US and Switzerland. Clinical trials showed that intravenous trabectedin was effective in chemotherapy-experienced patients with advanced, recurrent liposarcoma or leiomyosarcoma, and results from a retrospective analysis suggest that the drug may be particularly effective in patients with advanced myxoid liposarcoma. In addition, coadministration of trabectedin with pegylated liposomal doxorubicin was associated with a significantly longer progression-free survival (6 weeks) than pegylated liposomal doxorubicin monotherapy in patients with recurrent ovarian cancer after failure of first-line, platinum-based chemotherapy. The tolerability profile of trabectedin was manageable in clinical trials, and the tolerability profile of concomitant trabectedin and pegylated liposomal doxorubicin was generally consistent with that of each agent alone. Results to date indicate that trabectedin is a valuable addition to the group of second-line antineoplastic agents available for the treatment of advanced, recurrent STS, and that it is a beneficial treatment for recurrent ovarian cancer after failure of first-line, platinum-based chemotherapy when administered in conjunction with pegylated liposomal doxorubicin.