The analysis of panels of molecular biomarkers offers valuable diagnostic and prognostic information for clinical decision making. Robust, practical platforms that detect low levels of biomolecules (< 1000 copies) are urgently needed to advance medical care by diagnosing and predicting the progression of cancer and other disease states. Electrochemical methods providing low cost and direct biomarker read-out have attracted a great deal of attention for this application, but have, to date, failed to provide clinically-relevant sensitivity. We exploit controlled nanostructuring of electrode surfaces to promote surface accessibility and enhance capture rate and efficiency to solve this long-standing problem, and showed that the nanoscale morphologies of electrode surfaces control their sensitivities (Nature Nanotechnol., 2009). In addition, we have worked towards integrating nanomaterials-based electrodes into a chip-based platform to facilitate multiplexed analysis in a robust, practical format. Recently, we have developed an assay that isable to detect nucleic acids, proteins and small molecules, with universally high sensitivity levels. Our efforts to use these components to detect markers in clinical samples to develop tests for infectious disease diagnosis, oncological management and transplant medicine will be featured in this lecture.