ATP-citrate lyase (ACLY) is a cytosolic enzyme that catalyzes generation of acetyl-CoA from citrate. Acetyl-CoA is a vital building block for the endogenous biosynthesis of fatty acids and cholesterol and is involved in isoprenoid-based protein modifications. Acetyl-CoA is also required for acetylation reactions that modify proteins such as histone acetylation. In the present review some of the known features of ACLY such as tissue distribution, subcellular localization, enzymatic properties, gene regulation and associated physiological conditions are highlighted.