The therapeutic armamentarium for advanced soft tissue sarcoma (STS) has increased over the last few years. Doxorubicin monotherapy or in combination is now the established first line treatment. Beyond first line treatment, no standard therapy has been established. Novel drugs have reached the late-clinical stage development demonstrating to be effective in controlled studies. While these novel treatments can be beneficial to a subset of patients, even producing long lasting remissions, a significant fraction of the STS population derives limited benefit. This is due to the fact that STS is a very heterogeneous disease with different histopathologic features, biological characteristics and clinical behaviour. Areas covered: The primary aim of this review is to summarize data from recent phase III clinical trials in unselected STS population, and to discuss their impact on the current clinical practice. Phase I-II trials of special interest are discussed as well. Expert commentary: Although our efforts in this research task are ongoing, the integration of biological therapies, the anti-angiogenesis targeted treatments as well as immunotherapy that may further improve the long term control of advanced STS are of special clinical interest. Clinical management of advanced STS should be tailored to each patient in order to optimize therapy.