The median survival of women with advanced or recurrent endometrial cancer is less than one year. Of the women with early stage endometrial cancer and poor prognostic factors like high grade or deep myometrial invasion, 40% will recur. Over the last decade, incredible strides have been taken in evaluating systemic therapy for this disease, however, survival rates remain poor. Progestin therapy offers a 10 - 20% response rate and survival of less than one year. Progestins are most effective in women with well-differentiated tumours and long disease-free interval. There is no role for adjuvant progestin therapy in early stage disease. Single-agent chemotherapy with most activity include ifosfamide, cisplatin/carboplatin, doxorubicin and paclitaxel. Combination chemotherapy provides a response rate of 40 - 60%, however, median survival is still less than a year. New areas of research include the identification and evaluation of new active endocrine therapies (i.e., LY-353381.HCl and letrozole), chemotherapeutics (i.e., paclitaxel), evaluating chemotherapeutic agents in combination (i.e., paclitaxel, doxorubicin and platinum), in addition to radiation or instead of radiation. New avenues under development involve the specific molecules and pathways responsible for the initiation and growth of endometrial carcinoma (i.e., Herceptintrade mark). Exciting developments in the understanding of the molecules involved in tumour development and metastasis will allow the development of specific and selective inhibitors.