End-stage renal disease (ESRD) is associated with a significant propensity for development of atherosclerosis and cardiovascular mortality. The atherogenic diathesis associated with ESRD is driven by inflammation, oxidative stress, and dyslipidemia. Reduced high-density lipoprotein cholesterol (HDL-C) level and high-density lipoprotein (HDL) dysfunction are the hallmarks of ESRD-related dyslipidemia. Clinical and laboratory studies have revealed that ESRD is associated with significantly reduced serum apolipoprotein A-I (ApoA-I) and HDL-C level as well as altered HDL composition. Furthermore, although ESRD is associated with impaired HDL antioxidant and anti-inflammatory properties in most patients, in a small subset, HDL may in fact have a pro-oxidant and proinflammatory effect. Therefore, it is no surprise that serum HDL-C level is not a dependable indicator of cardiovascular disease burden in ESRD, and markers such as HDL function are critical to accurately identifying patients at risk for cardiovascular disease and mortality in ESRD.