CXC chemokine ligand 16 (CXCL16) is a CXC soluble chemokines, an adhesion molecule and a cell surface scavenger receptor. CXCL16 regulates inflammation, tissue injury and fibrosis. Parenchymal renal cells, vascular wall cells, leukocytes and platelets express and/or release CXCL16 under the regulation of inflammatory mediators. CXCL16 expression is increased in experimental and human nephropathies. Targeting CXCL16 protected from experimental glomerular injury or interstitial fibrosis. Conflicting results were reported for experimental cardiovascular injury. High circulating CXCL16 levels are associated to human kidney and cardiovascular disease and urinary. CXCL16 may increase in kidney injury. In conclusion, mounting evidence suggests a role of CXCL16 in kidney and cardiovascular disease. However, a better understanding is still required before exploring CXCL16 targeting in the clinic.