Proteomic biomarkers offer the hope of improving the management of patients with kidney diseases by enabling more accurate and earlier detection of renal pathology than is possible with currently available biomarkers, serum creatinine and urinary albumin. In addition, proteomic biomarkers could also be useful to define the most suitable therapeutic targets in a given patient or disease setting. This Review describes the current status of proteomic and protein biomarkers in the context of kidney diseases. The valuable lessons learned from early clinical studies of potential proteomic biomarkers in kidney disease are presented to give context to the newly identified biomarkers, which have potential for actual clinical implementation. This article also includes an overview of protein-based biomarker candidates that are undergoing development for use in nephrology, focusing on those with the greatest potential for clinical implementation. Relevant issues and problems associated with the discovery, validation and clinical application of proteomic biomarkers are discussed, along with suggestions for solutions that might help to guide the design of future proteomic studies. These improvements might remove some of the current obstacles to the utilization of proteomic biomarkers, with potentially beneficial results.