This brief overview of studies into the urine proteome illustrates its potential value for diagnostic, prognostic, and pathophysiologic discovery. Hypothesis-targeted investigations of individual proteins as well as proteome-wide searches for urinary biomarkers of various diseases and their progression are reviewed. The majority of urine proteins appear as cleavage products that are found not only as free solutes but also in secreted membrane vesicles called exosomes. Described are several recent examples of important diagnostic findings using urine proteomics along with the idea that signature profiles of injury to individual nephron segments can be measured by this technology. Shared are some thoughts on the most challenging step: Integration of seemingly unrelated findings of various protein fragments into a rational pathogenetic pathway(s). The future chance that the centuries-old technique of uroscopy will reveal its secrets using modern proteomic approaches makes gradual improvement.