(1) NPs interact with or modify plasma membrane and therefore change the membrane structure and induce membrane permeability; (2) NPs do not enter cells; instead free drugs are released to plasma membrane and then diffuse into cells; (3) NPs directly interact with and inhibit P-gp; (4) NPs bypass, but do not inhibit P-gp; (5) NPs enter into cells via receptor-mediated endocytosis; (6) NPs enter into cells via endocytosis, phagocytosis, or micropinocytosis; (7) NPs down-regulate P-gp, MRP, BCL-2, and HSP-70; (8) NPs up-regulate BAX, p53, and caspase-3; (9) NPs generate ROS; (10) NPs deplete ATP; (11) Very small NPs enter into the nucleus; (12) NPs dysregulate mitochondrial function or activate mitochondrial independent apoptotic pathways.