Kidney failure leads to the uremic syndrome that is the clinical expression of the malfunction of vital organs due to the accumulation of uremic toxins, which are normally cleared by the kidneys. Progressively more uremic retention solutes have been identified and their potential toxicity has been characterized. Polypeptides constitute a heterogeneous group of uremic molecules. Therefore, proteome analysis represents a new and promising analytical approach to identify new uremic toxins. Proteomic technologies cover applicability to a broad molecular mass range. For polypeptides >10 kDa classical proteomic techniques, such as two-dimensional gel electrophoresis followed by mass spectrometry, are able to identify uremic polypeptides. In the mass range from approximately 1 to 10 kDa, capillary electrophoresis coupled to mass spectrometry (CE-MS) emerged as a fast possibility to analyze of up to 1,400 compounds in a single step. This chapter will provide an overview about proteomic technologies as efficient tools for the detection of uremic toxins, emphasizing the features of CE-MS. Subsequently, examples of the application of proteomic techniques to define novel biomarkers for renal diseases and uremic toxins will be discussed.