Lipase-catalyzed reactions of polar substrates are inefficient in organic solvents. Nonpolar organic solvents do not dissolve polar substrates, while polar organic solvents inactivate lipases. Ionic liquids such as 1-alkyl-3-methyl imidazolium tetrafluoroborate are as polar as N-methyl formamide or methanol, but, unlike these solvents, ionic liquids do not inactivate lipases. This unusual feature creates opportunities for nonaqueous biocatalysis with polar substrates. First, we describe a simple purification involving filtration through silica gel, which yields ionic liquids that work reliably as solvents in lipase-catalyzed reactions. Next, we report two examples that exploit these unique advantages of ionic liquids. First, lipase-catalyzed acetylation of glucose was up to twelve times more regioselective in ionic liquids than in acetone. Second, lipase catalyzed the acylation of ascorbic acid to make fat-soluble antioxidants. In some cases, reactions in ionic liquids were comparable or slower than in tert-amyl alcohol, but in typical cases, the reactions in ionic liquids were twice as fast and proceeded to higher conversion. Ionic liquids also offer the possibility to use vacuum to remove water formed by the esterification and drive the equilibrium even further toward product.