Soft tissue sarcomas (STS) are heterogeneous, mesenchymal malignancies with variable biologic behavior. The primary management for localized STS is surgical resection, which may be combined with neoadjuvant or adjuvant radiation therapy to increase the probability of achieving local control. Many patients with large, high-grade STS develop metastatic disease. Several clinical trials of immune checkpoint blockade for STS have produced promising responses in patients with metastatic disease. In this review, recent and ongoing clinical trials of immune checkpoint inhibition for STS are discussed. The authors explain the rationale for immune checkpoint inhibition and radiation therapy and highlight new studies testing this combination in the neoadjuvant setting for patients with high-risk STS. In addition, they describe novel combinations of immunotherapy with targeted therapies and chemotherapies being tested in the metastatic setting and discuss how these combinations have the potential to be integrated into adjuvant therapy in the future.