Nanoparticle science is rapidly changing the landscape of various scientific fields and defining new technological platforms. This is perhaps even more evident in the field of nanomedicine whereby nanoparticles have been used as a tool for the treatment and diagnosis of many diseases. However, despite the tremendous benefit conferred, common pitfalls of this technology is its potential short and long-term effects on the human body. To understand these issues, many scientific studies have been carried out. This review attempts to shed light on some of these studies and its outcomes. The topics that were examined in this review include the different possible uptake pathways of nanoparticles and intracellular trafficking routes. Additionally, the effect of physicochemical properties of nanoparticle such as size, shape, charge and surface chemistry in determining the mechanism of uptake and biological function of nanoparticles are also addressed.