Metabolomics has been increasingly applied to study renal and related cardiometabolic diseases, including diabetes and cardiovascular diseases. These studies span cross-sectional studies correlating metabolites with specific phenotypes, longitudinal studies to identify metabolite predictors of future disease, and physiologic/interventional studies to probe underlying causal relationships. This chapter provides a description of how metabolomic profiling is being used in these contexts, with an emphasis on study design considerations as a practical guide for investigators who are new to this area. Research in kidney diseases is underlined to illustrate key principles. The chapter concludes by discussing the future potential of metabolomics in the study of renal and cardiometabolic diseases.