Abstract: Surgery is the definitive treatment for soft tissue sarcomas of the extremities and trunk, but is often unable to achieve long-term disease control in high-risk patients. The dominant mode of treatment failure is distant metastasis, with local relapse being secondary. Some patients with advanced local disease may be unresectable, or marginally so, and consequently face a poor prognosis.Peri-operative systemic therapy and radiotherapy may be able to enhance outcomes of surgical treatment. Peri-operative systemic therapy has been challenging to validate. Systemic therapy can lead to decreased tumor sizes. Validation of local control benefits in facilitating more conservative surgical procedures remains incomplete. For those with primary tumors judged difficult or impossible to resect, neoadjuvant chemotherapy may provide a route to local disease control.Peri-operative systemic therapy may also prevent development of metastatic disease. A recent study suggested benefit from adjuvant therapy with anthracycline/ifosfamide-based therapy, albeit in a post hoc reanalysis of a large trial. A randomized trial of neoadjuvant systemic therapy suggested that anthracycline/ifosfamide-based therapy may improve disease-free and overall survival in selected histologic sarcoma subtypes. This effect appeared mediated by improved distant metastasis-free survival, rather than improved local control. Methodological limitations in both trials necessitate further investigation. Nevertheless, we believe the results support the use of neoadjuvant systemic therapy in management of locally advanced soft tissue sarcomas of the extremities and trunk. Radiotherapy has a well-established position in conjunction with surgery for sarcomas treatment. While outcomes do not seem to vary depending on sequencing of radiotherapy administration versus surgery, adverse effects do so. Adjuvant radiotherapy is associated with lower peri-operative wound complication rates than neoadjuvant therapy, but the higher radiation doses required for adjuvant treatment yield long-term functional outcomes inferior to neoadjuvant radiotherapy. For this reason, we believe that peri-operative radiotherapy, like systemic therapy, should be administered neoadjuvantly, when possible.