Chronic kidney disease (CKD) represents a major challenge to public healthcare. Traditional clinical biomarkers of renal function (blood urea nitrogen and serum creatinine) are not sensitive or specific enough and only increase significantly after the presence of substantial CKD. Therefore, more sensitive biomarkers of CKD are needed. CKD-specific biomarkers at an early disease stage and early diagnosis of specific renal diseases would enable improved therapeutic treatment and reduced the personal and financial burdens. The goal of metabolomics is to identify non-targeted, global small-molecule metabolite profiles of complex samples, such as biofluids and tissues. This method offers the potential for a holistic approach to clinical medicine, as well as improvements in disease diagnoses and the understanding of pathological mechanisms. This review article presents an overview of the recent developments in the field of metabolomics, followed by an in-depth discussion of its application to the study of CKD (primary, chronic glomerulonephritis such as IgA nephropathy; secondary, chronic renal injury such as diabetic nephropathy; chronic renal failure including end-stage kidney disease with and without undergoing replacement therapies, etc), including metabolomic analytical technologies, chemometrics, and metabolomics in experimental and clinical research. We describe the current status of the identification of metabolic biomarkers in CKD. Several markers have been confirmed across multiple studies to detect CKD earlier than traditional clinical chemical and histopathological methods. The application of metabolomics in CKD studies provides researchers the opportunity to gain new insights into metabolic profiling and pathophysiological mechanisms. Particular challenges in the field are presented and placed within the context of future applications of metabolomic approaches to the studies of CKD.