Nanoparticles (NPs) are being extensively used in the field of nanomedicines. Different types of NPs are administered into the body by various routes. NPs come in contact with cells inside the body. Cellular response of NPs is affected by size, shape, surface chemistry, and cellular uptake pathways of NPs. In addition to this, type of cells, various cell lines, and growth media are also found to affect the cellular response of NPs. NPs induce diverse cellular responses like apoptosis, necrosis, and reactive oxygen species (ROS) production. NPs also form a protein corona inside the biological media which may alter their identity and behaviour as compared to bare NPs. In this chapter, we have made an attempt to throw light on cellular uptake pathways of NPs, monitoring of endocytic pathways followed by NPs, factors affecting cellular responses of therapeutic NPs, and protein corona formation, characterisation and its implications on fate of NPs.