Nanoparticles have promising biomedical applications for drug delivery, tumor imaging and tumor treatment. Pharmacokinetics are important for the in vivo application of nanoparticles. Biodistribution and clearance are largely defined as the key points of pharmacokinetics to maximize therapeutic efficacy and to minimize side effects. Different engineered nanoparticles have different biodistribution and clearance processes. The interactions of organs with nanoparticles, which are determined by the characteristics of the organs and the biochemical/physical properties of the nanoparticles, are a major factor influencing biodistribution and clearance. In this review, the clearance functions of organs and the properties related to pharmacokinetics, including nanoparticle size, shape, biodegradation and surface modifications are discussed.