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Liposarcoma is the most common soft tissue sarcoma. With its various subtypes, the natural history of this disease can vary significantly from a locally recurrent tumor to a highly malignant one carrying a poor prognosis. Progress in the understanding of the specific molecular abnormalities in liposarcoma provides greater opportunity for new treatment modalities. Although surgical resection and radiation therapy remain the keystones for the management of primary liposarcoma, the inclusion of novel agents that target known abnormalities in advanced liposarcoma enhances the potential for improved outcomes.