The completion of the human genome project has led to intensified efforts toward comprehensive analysis of proteomes. New possibilities exist for efficient proteomic technologies. However, primary attention is given to the discovery of new predictive biomarker patterns. Understanding proteomes and, in particular, protein-mediated interactions underlying their complexity and diversity, is critical for the development of more reliable and robust diagnostic platforms, which are anticipated to enable personalized medicine. Of immediate relevance in this respect are those approaches that capitalize on the application of nanotechnology, which is seen as a powerful tool for the diagnosis of early-stage diseases. Here we highlight the current state of the field exemplified by recent nano-enabled technologies for biomarker discovery.