The multifactorial glycoprotein, adiponectin has demonstrable insulin-sensitizing, anti-atherogenic and anti-inflammatory properties. However, despite the prevalence of both insulin-resistance and vascular disease in patients with end-stage kidney disease, levels of adiponectin are high. Adiponectin circulates in different sizes (the high-molecular-weight (HMW) isoform is thought to be the most insulin-sensitizing type) and binds to two receptors, adiponectin receptors (AdipoR) 1 and 2. The adiponectin/receptor system appears to be upregulated in end-stage kidney disease possibly as an appropriate counter-regulatory response to the uraemic milieu. In contrast, adiponectin and its HMW isoform, AdipoR mRNA expression on peripheral blood mononuclear cells decrease after kidney transplantation, likely secondary to immunosuppression and/or an improvement in glomerular filtration rate and the uraemic environment. Adiponectin has also been detected in the urine of patients with proteinuric kidney disease. The presence of AdipoR on an immortal cell line of proximal tubular epithelial cells (HK-2) and an increased amount of intact HMW isoform in the urine of patients with various forms of proteinuria lead us to speculate about the potential role of urinary adiponectin. This review will also discuss the structure and function of adiponectin and its potential relevance to patients with kidney disease and the different factors that may influence the metabolism of this protein in kidney failure.