Lipoprotein lipase, hepatic lipase, and endothelial lipase are sn-1 lipases that play important roles in the metabolism of plasma lipoproteins. In vitro and in vivo studies suggest that these lipases exhibit both pro- and anti-atherogenic properties, which are dependent primarily on their tissue localization. The following chapter reviews the physiology of these lipases, and the consequences of the loss or gain of function for each lipase in modulating atherosclerosis, with emphasis on murine models.