Chronic kidney disease (CKD) is now considered as one of the strongest risk factors for all cause mortality and cardiovascular events. However, the link between CKD and systemic events is unclear. The role of the kidney is primarily considered a target organ during the development of obesity as altered production of adipokines from visceral adipocytes, however, it should also be recognized that the kidney itself could alter the clearance and production of adiopokines. In this chapter, we provide a discussion of renal handling of a variety of adipokines. Specifically, there is a growing body of data supporting a major role for the kidney in clearance of insulin, leptin, and TGF-β. In addition, plasminogen activator inhibitor-1, vascular endothelial growth factor, angiotensin II, and resistin may also be altered by the kidney. The mechanistic regulation of renal handling by the kidney of a variety of circulating adipokines, however is poorly defined. We conclude that the kidney has pivotal roles in the regulation of adipokines and that altered renal handling of adipokines may contribute to the imbalance of factors that ultimately lead to progressive cardiovascular and systemic disease.