The field of molecular medicine is moving beyond genomics to proteomics and a systems biology approach to disease. While DNA is the information archive, proteins do all the work of the cell and ultimately dictate all biological processes. It is the proteins themselves that are most often the drug targets, especially in the new era of personalized therapy where cellular “circuitry” is being targeted. These pathways consist of protein networks, not genes, and these networks are controlled by processes that cannot be predicted by genetic analysis. The future of patient-tailored therapy will rely on new proteomic approaches to discover and profile cellular “circuitry” within a tiny biopsy specimen. Liotta and Petricoin have developed a cadre of new technologies and approaches to translational medicine whereby ex-vivo molecular targeting takes place as an entrée into patient selection and personalization of therapy.