Display omitted •Clearance routes of nanoparticles in the lung are presented.•Factors influencing nanoparticle transaction are discussed.•Physicochemical properties of the nanoparticles could influence their fate in the lung. The inhaled delivery of nanomedicines has attracted much attention in the treatment of lung diseases or systemic diseases. However, there is a lack of understanding about their fate upon lung delivery. Thus, the objective of this review is to summarize physicochemical properties affecting the fate of nanoparticles after deposition in the lung. First, physiological structure and characteristics of the lung are described. Thereafter, physicochemical properties that could influence the clearance and translocation of nanoparticles in the lung are discussed, including particle size, surface charge and surface hydrophilicity. It is believed that, with a better understanding of the fate of nanoparticles in the lung, it will broaden their application in inhalation for a better therapeutic effect in the future.