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Objective:To describe the role of proteomic profiling in the diagnosis and treatment of ovarian cancer.Methods:We report a thorough review of the literature, ongoing trials, and our group's experience with proteomic profiling for early detection, recurrence, and treatment of ovarian cancer.Results/Conclusions:Ovarian cancer remains the deadliest gynecologic malignancy in the western world and is most often diagnosed at a rarely curable late stage. Novel applications of proteomic techniques, such as mass spectrometry, show promise in the quest for reliable multimodality screening programs for the early detection of ovarian cancer. Proteomic analysis of tissue samples has underscored the heterogeneity of this disease process. Development of validated assays that survey the genetic and/or proteomic makeup of an individual tumor will add greatly to the histological classification of the tumor and may lead to different treatment approaches tailored to the unique expression pattern of each individual patient. As novel agents that disrupt signal propagation develop, proteomic profiling by reverse-phase protein arrays can characterize the in-tumor efficacy of the agent by quantification of the changes in expression levels of activated proteins. Together, better understanding of the potential diagnostic and therapeutic targets followed with proof-of-target effect will lead to rational combinations of novel therapy and improve individual ovarian cancer patient outcome.