In the era of targeted therapies, patients with gynecologic malignancies have not yet been major beneficiaries of this new class of agents. This may reflect the fact that the main tumor types-ovarian, uterine, and cervical--are a highly heterogeneous group of cancers with variable response to standard chemotherapies and the lack of models in which to study the diversity of these cancers. Cancer-derived cell lines fail to adequately recapitulate molecular hallmarks of specific cancer subsets and complex microenvironments, which may be critical for sensitivity to targeted therapies. Patient-derived xenografts (PDX) generated from fresh human tumor without prior in vitro culture, combined with whole genome expression, gene copy number, and sequencing analyses, could dramatically aid the development of novel therapies for gynecologic malignancies. Gynecologic tumors can be engrafted in immunodeficient mice with a high rate of success and within a reasonable time frame. The resulting PDX accurately recapitulates the patient's tumor with respect to histologic, molecular, and in vivo treatment response characteristics. Orthotopic PDX develop complications relevant to the clinic, such as ascites and bowel obstruction, providing opportunities to understand the biology of these clinical problems. Thus, PDX have great promise for improved understanding of gynecologic malignancies, serve as better models for designing novel therapies and clinical trials, and could underpin individualized, directed therapy for patients from whom such models have been established.