Many challenges exist with disease-state biomarker identification. These challenges include sample heterogeneity, poorly designed sample sets, insufficient numbers of samples, as well as inconvenient workflows, inadequate methodology, and development of false-positive markers resulting from protein degradation during sample handling. Yet despite these difficulties, substantial progress has been achieved with the application of proteomic methods toward biomarker discovery in renal disease. Significant advances have occurred in the past decade with electrophoretic, chromatographic, and mass spectrometric methods for discerning biomarkers of disease. Recent applications of proteomics to the study of renal disease have identified new mechanisms in renal disease progression and established protein expression profiles for complex renal diseases including glomerular and tubular pathologies. In some cases these protein profiles have proven successful with guiding patient treatment and markers for pharmacologic therapies. Proteomic analysis only recently has been applied to the study of renal disease, yet it has shown substantial potential for future successes.