High-risk soft tissue sarcomas (STS) are defined as large (>5 cm), intermediate/high-grade tumors and can carry a >50 % risk of death from metastases. A regimen of preoperative chemoradiation immediately addresses issues of both local control and micrometastases and should be considered for patients with high-risk STS of the extremities. While acute wound healing complications are more likely to occur, these are most always manageable and reversible, as opposed to the long-term complications associated with higher radiation doses and larger fields required for post-operative therapy. Preoperative treatment also yields potential prognostic information from pathologic treatment response, and quantitative imaging methods hold promise to detect early treatment effect. Definitive evidence of survival benefit from neoadjuvant therapy has been elusive, but a large body of experience has accumulated at dedicated centers where this approach is utilized. Whenever possible, it is imperative that patients with high-risk STS be enrolled on well-designed clinical trials. Treatment planning and administration requires a coordinated multidisciplinary approach that should be undertaken in high-volume centers with expertise in the management of sarcomas.