High-grade undifferentiated sarcomas (HGUS) are rare malignancies accounting for 6 % of all uterine sarcomas and have a very poor outcome. Histological classification of HGUS is currently debated as a subgroup with uniform nucleoli, and frequently YWHAE-FAM22 transcript has been described, constituting a potential target for new therapies. In localized HGUS, surgery involving total hysterectomy and bilateral oophorectomy is recommended. Adjuvant radiotherapy has recently been suggested in a retrospective study to decrease local recurrence and improve survival versus observation in localized HGUS. In metastatic or recurrent disease, chemotherapy with doxorubicin with or without ifosfamide constitutes the standard of care. Gemcitabine plus docetaxel also seems to be an interesting alternative. Targeted therapies such as pazopanib are now available for soft tissue sarcomas and so could be proposed for uterine sarcoma patients after first- or second-line chemotherapy in the metastatic phase. Further investigations are needed to determine their indications and targets. A European Organisation for Research and Treatment of Cancer (EORTC) randomized trial testing maintenance therapy with cabozantinib after first-line chemotherapy in HGUS is ongoing.