The development of noninvasive methods for diagnosis and prognosis of many diseases still remains a challenging task in clinical medicine. In recent years, protein separation and detection techniques have been refined such that they allow proteome screening of biological fluids with good reproducibility, accuracy, and real-time performance. The advancements in this field resulted in the initiation and conduction of many clinical studies aimed towards defining sensitive and selective biomarkers for disease or a pathological condition. In this review, we focus on the description of the state of the art proteomic platforms established or adapted to use urine as sample source for biomarker discovery. In the second part of this review, we will give an overview of recent clinical studies that used capillary electrophoresis-mass spectrometry (CE-MS) in urinary proteomics/peptidomics. Owing to its fast and accurate one-step screening method CE-MS allows resolution of the urinary small molecular weight proteome in high-throughput mode. This makes CE-MS well suited for use in large proteomic studies. The fact that urinary proteomic studies are not restricted to renal and urological disorders, but also enable assessment of systemic diseases like cardiovascular or infectious diseases, clearly demonstrates the considerably high potential that urine offers for biomarker discovery and for diagnosis, staging, prognosis, and progression monitoring of diseases.