Ovarian cancer is the leading cause of death from gynecologic malignancies among American women and the fourth most frequent cause of death from cancer in women in Europe and the US. Despite appropriate surgical and chemotherapeutic intervention, the 5-year survival in patients with metastatic cancer remains poor. Currently available screening methods, including CA125, additional biomarkers, and transvaginal ultrasound lack the necessary sensitivity and specificity to provide accurate and cost-efficient screening for the general population or the ability to assess who will benefit most from each treatment. These limitations have prompted the study of proteomic technology and its application in ovarian cancer diagnostics. Proteomics is the study of molecules in the functional protein pathways of normal or diseased states. Clinical trials are currently being conducted to assess the sensitivity and specificity of serum proteomic patterns and additional clinical trials are designed to evaluate the effects of molecularly targeted agents on protein signaling pathways in human subjects. Overcoming both scientific and practical limitations will lead to increased knowledge of deranged protein networks in cancer cells. Clinical trials in proteomics may result in improved early detection, better monitoring, new drugs and molecularly targeted therapeutics, and individualized therapies.