Adiponectin, an anti-inflammatory, anti-atherogenic and insulin sensitizing adipokine exists in several isoforms in the circulation. In patients with chronic kidney disease (CKD), circulating levels of total as well as high-molecular-weight adiponectin are elevated. In contrast to initial studies, several recent and larger studies on outcomes do not support a protective effect of high adiponectin on cardiovascular disease (CVD) and overall mortality in CKD patients. Paradoxically, high adiponectin predicts increased overall and cardiovascular mortality in CKD patients. This effect seems unrelated to a direct effect of adiponectin, but rather due to a process of protein-energy (PEW) wasting. This review summarizes recent conflicting findings on adiponectin in relation to outcomes and discusses the pathophysiologic roles of adiponectin in PEW, insulin resistance and vascular injuries of CKD patients.