Despite several decades of intensive research and hard work in nephrology, a void exists in the availability of markers for identifying at-risk individuals, diagnosing diseases at incipient stage, and predicting treatment response. Most of the current widely available diagnostic tools such as creatinine, urine analysis, and imaging studies are quite insensitive such that about half of the kidney function is lost before perceivable changes are observed with these tests. In addition, these parameters are affected by factors other than renal, questioning their specificity. Renal biopsy, though specific, is quite expensive, risky, and invasive. The recent surge in the knowledge of small molecules in the tissue and body fluids, "metabolomics," thanks to the Human Metabolome Database created by the Human Metabolome Project, has opened a new avenue for better understanding the disease pathogenesis and, in parallel, to identify novel biomarkers and druggable targets. Kidney, by virtue of its metabolic machinery and also being a major handler of metabolites generated by other tissues, is very much amenable to the metabolomic approach of studying its various perturbations. The gut microbiome, characterized by the Human Microbiome Project, is one of the principal players in metabolomics. Changes in metabolite profile due to alterations in gut microbiome can occur either as a cause or consequence of renal diseases. Unmasking the renal-metabolome-microbiome link has a great potential to script a new era in the diagnosis and management of renal diseases.