Lipoproteins consist of lipids and apolipoproteins that have functional roles in lipid metabolism. It has been suggested that oxidation of lipoproteins by reactive oxygen species (ROS) may be involved in the inception of various diseases. In particular, the relationship between low-density lipoprotein (LDL) oxidation and atherosclerosis has been studied in great detail. The main target molecules of lipoprotein oxidation are polyunsaturated fatty acid residues of lipids and apolipoproteins. Extensive investigations have characterized oxidative modifications of apolipoprotein B100 (apo B100) in LDL. Furthermore, modifications of apo B100 by oxidized lipids have been confirmed in oxidized LDL and atherosclerotic lesions using immunological techniques. In this chapter, characteristics and oxidation mechanisms of lipoproteins by ROS are described from in vitro and in vivo studies. Oxidative modifications of apo B100 by lipid hydroperoxides, major products of lipid peroxidation at the early stage, are principally reported.