Patients with advanced metastatic soft tissue sarcoma (STS) have a poor prognosis, and in the last two decades of the 20th century their overall survival has remained unchanged. Improved treatments are needed for these patients and for preventing metastases in earlier stages of disease. Numerous novel agents and new combination regimens are undergoing clinical testing in STS. Some of these agents show promising activity. Pazopanib is one such agent that has undergone Phase II and III evaluations in advanced STS. Pazopanib is a multi-tyrosine kinase inhibitor, blocking various signaling pathways, thereby preventing angiogenesis and metastasis, and inhibiting tumor cell growth and survival. In a Phase II study, pazopanib demonstrated activity in patients with advanced leiomyosarcomas, synovial sarcomas and other eligible STSs. This activity was confirmed in a Phase III trial, where pazopanib significantly extended the median progression-free survival versus placebo in a variety of STS subtypes.