Both epidemiological and toxicological studies indicate that inhalation and subsequent deposition of air borne particles into the lungs have adverse health effects. Recently, the ultrafine particle (UfP) fraction (diameter < 100nm) has received particular attention, as their small size may lead to more toxic proper ties. In this study we summarize the current knowledge on the dosimetry of inhaled particles (including UfPs) with a focus on recent data on translocation of UfPs into secondary target organs (such as brain and heart) suggesting that the lifetime dose of ambient UfPs in secondary target organs is about 1011 particles. Furthermore, we highlight the main pathways of particle induced toxicity and the reasons for the potentially higher toxicity of UfPs. Finally, we discuss recent evidence indicating that (BET) surface area is the single most relevant dose metric for the toxicity of UfPs, which has important implications for regulatory measures on the toxicity of ambient and engineered particles.