Wide surgical excision is the backbone of therapy for localized soft tissue sarcoma and often produces excellent results. Patients with a marginal resection of disease and high-grade or large tumors are at an increased risk of recurrence. Radiation therapy (external beam or brachytherapy) has been shown to reduce the risk of local recurrence of disease and should be offered to patients with large (>5 cm) or high-grade sarcomas, especially if a wide resection cannot be performed. Use of preoperative versus postoperative radiation therapy should be planned, in consultation with a radiation oncologist and a surgical oncologist, before resection of the sarcoma if possible. Chemotherapy using an anthracycline- and ifosfamide-based regimen may improve disease-free and overall survival rates. Chemotherapy appears to be most beneficial for patients with very large (≥10 cm), high-grade sarcomas of the extremity who are at a high risk of experiencing distant recurrence of disease. The effect of adjuvant chemotherapy on overall survival remains controversial. Research is greatly needed to identify the patients who are most likely to benefit from conventional chemotherapy, improve the treatment of retroperitoneal sarcomas, and identify novel agents that may impact the natural history of high-risk soft tissue sarcoma.