Exposure of human skin to nanoparticles (NPs) is increasing with the development of nanotechnology and new applications of NPs in medicine. Safety concerns have sparked debate on the capacity of NPs to penetrate through skin and enter into the body. This article attempts to summarize the recent evidence on whether NPs penetrate human skin and the factors that may affect the penetration. Skin structure and penetration mechanisms are reviewed to provide background information. Size, shape, formulation, surface properties and application methods and their effects on skin penetration are specifically discussed. Finally, the relationship between skin penetration and nanotoxicity is reviewed to further emphasise the importance of the research in this area.