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The increase in progressive kidney disease, resulting in a constantly rising prevalence of endstage renal disease (ESRD), urgently warrants the development of more effective strategies to diagnose, prevent, and intervene in renal disease. Histological information obtained by renal biopsies (RBx) is a cornerstone of the current management of kidney disease. Renal tissue can provide critical information on the disease process not available by nontissue-based approaches. However, insight gained by conventional histopathology remains limited and additional strategies to define renal disease on a molecular level are required. The sequencing of the human genome, together with recent advances in genome-wide profiling techniques, has provided the framework for a comprehensive analysis of renal disease-associated transcriptional programs. In this review, strategies to apply these technological advances towards the analysis of RBx will be described, with special emphasis on their potential impact on clinical management, but also on their inherent limitations. Finally, an outlook towards the emerging proteomic studies of renal disease will be given.