Endothelial lipase (EL) is a phospholipase that belongs to the lipoprotein lipase (LPL) family, which includes LPL and hepatic lipase (HL). Similar to LPL and HL, EL regulates lipoprotein metabolism, mainly high-density lipoprotein (HDL) metabolism and HDL cholesterol (HDL-C) levels in humans and mice. Existing data strongly suggest that inhibition of EL in humans would be expected to increase the HDL-C level. However, it has not been definitively established whether the effect of EL activity on HDL-C levels translates into effects on reverse cholesterol transport or atherosclerosis. The available data regarding the impact of EL expression and activity on HDL metabolism, reverse cholesterol transport, and atherosclerosis are reviewed.