The interactions of nanoparticles with the soft surfaces of biological systems like cells play key roles in executing their biomedical functions and in toxicity. The discovery or design of new biomedical functions, or the prediction of the toxicological consequences of nanoparticles in vivo, first require knowledge of the interplay processes of the nanoparticles with the target cells. This article focusses on the cellular uptake, location and translocation, and any biological consequences, such as cytotoxicity, of the most widely studied and used nanoparticles, such as carbon-based nanoparticles, metallic nanoparticles, and quantum dots. The relevance of the size and shape, composition, charge, and surface chemistry of the nanoparticles in cells is considered. The intracellular uptake pathways of the nanoparticles and the cellular responses, with potential signaling pathways activated by nanoparticle interactions, are also discussed.