Cholesterol, an important biological lipid and excessive dietary intake, is associated with hypercholesterolemia, a prevalent cardiovascular risk factor. Because cholesterol is essentially a water insoluble molecule, its transport within and absorption from the aqueous medium of the intestine is rather complex. This takes place in a series of orderly and interrelated steps, including emulsification, hydrolysis by specific pancreatic esterases, micellar transport, mucosal absorption, resynthesis in enterocytes and assembly with apolipoproteins to form chylomicrons. Many of these processes are not well characterized at the molecular level. Besides being generally inefficient, cholesterol absorption is highly variable with a between-subject variability that depends in part on genetic factors and an intraindividual variability, which may be modulated by physiological and dietary conditions. All of the sequential steps in intestinal cholesterol absorption can be interfered with by dietary components or drugs and therefore are potential therapeutic targets for rendering cholesterol absorption even more inefficient in an attempt to lower cholesterol levels.