Over the two last decades, cloning of proteins responsible for trafficking and metabolic fate of long-chain fatty acids (LCFA) in gut has provided new insights on cellular and molecular mechanisms involved in fat absorption. To this systematic cloning period, functional genomics has succeeded in providing a new set of surprises. Disruption of several genes, thought to play a crucial role in LCFA absorption, did not lead to clear phenotypes. This observation raises the question of the real physiological role of lipid-binding proteins and lipid-metabolizing enzymes expressed in enterocytes. The goal of this review is to analyze present knowledge concerning the main steps of intestinal fat absorption from LCFA uptake to lipoprotein release and to assess their impact on health.