During the past decade, a new paradigm in cancer therapeutics has emerged that offers the promise of personalized medicine, where the individual characteristics of a patients tumor can be evaluated and exploited. In this setting, the primary site of malignancy would become a secondary consideration; rather it would be the fundamental driving factor, the 'molecular fingerprint of the tumor, that would determine the appropriate therapy. This concept of cancer therapy is still in its infancy, with prospective tumor genotyping being used on a limited, often experimental basis in specific disease sites such as the colon, breast and lung. As technology and understanding improve, many look forward to a time when all tumors can be interrogated for an array of known amplifications, mutations or deletions that drive neoplastic pathways and thus represent a potential Achilles heel that may confer sensitivity to targeted molecular therapies, and a better toxicity profile. This article will present the current state of ovarian cancer therapy, discuss a blueprint for applying targeted approaches, and address the challenges and future prospects for researchers and clinicians utilizing targeted agents for this deadly disease. © 2010 Expert Reviews Ltd.