The interactions between macromolecules and nanoparticles and cells involve the adhesion to the cell membrane, cellular uptake, distribution in the cell and exocytosis. Fully understanding these interactions is very important for apprehending the physiological process of the body and mechanism of drug action and gene therapy at the cellular level. In this paper, we first briefly describe the mechanism of endocytosis such as clathrin- or caveolae-mediated endocytosis, macropinocytosis, phagocytosis. Then the mechanism of cellular uptake of cell penetrating peptides (CPP) and their application is introduced. In succession, we discuss the pathway of nanoparticle entry into cells and effect of surface properties of nanoparticles on cellular uptake. Finally, the strategies of escape from the endosomes are briefly described.