There are multiple different subtypes of soft tissue sarcomas and each subtype has different characteristics and systemic therapy options. For localized disease, the role of neo-adjuvant and adjuvant therapy is debatable, and nomograms can be used to risk stratify patients while making decisions about neo-adjuvant and adjuvant systemic anti-cancer therapy. In the advanced disease setting, anthracycline-based chemotherapy (i.e. doxorubicin) constitutes the backbone of systemic therapy and is used as first-line therapy. Ifosfamide, gemcitabine, trabectedin, eribulin, docitaxel, and dacarbazine are other chemotherapies that have been shown to lead to clinical benefit in soft tissue sarcomas. More recently, targeted therapies were also shown to lead to better overall and progression-free survival in certain subtypes of soft tissue sarcomas due to a better understanding of the molecular characteristics of the disease. These include treatments such as NTRK inhibitors and EZH2 inhibitors. On the other hand, despite the success in other tumour types, checkpoint inhibitors have shown limited clinical benefit in soft tissue sarcomas. However, there is promising data on the efficacy of cellular therapy in certain subtypes such as synovial sarcoma but further studies are needed.