Abstract: Lipid nanoparticles have attracted increasing attention as potential drug carrier. The researches relating to surface modification of lipid nanoparticles become a hot spot during recent years. Through surface modification, the lipid nanoparticles could effectively decrease the phagocytosis by mononuclear phagocyte, prolong retention time in circulation, and achieve the active targeting to action site of drug. This review focused on in vivo fate of lipid nanoparticles and the developments of surface modification.