Leiomyosarcoma (LMS) is the most common soft tissue sarcoma in adults and can occur in any part of the body. Uterine leiomyosarcoma (uLMS) is the most common location for LMS, making up 2% to 5% of all uterine malignancies. It is an aggressive tumor that is challenging to treat because of its resistance to standard therapy. The majority of patients (60%) are diagnosed with early-stage disease. However, regardless of the stage, uLMS has a poor prognosis. Surgical resection is the cornerstone of treatment for patients with localized LMS independent of the site of origin. Adjuvant chemotherapy for early-stage disease remains controversial as multiple clinical trials have failed to demonstrate benefit on overall survival. Progress has been made in therapy for advanced and recurrent disease. This case study will highlight the current and emerging data regarding novel therapies for women with uLMS.