Current research overflows with instant proof of concept studies proposing nanoparticles for biomedical applications. The biological environment more or less hurriedly interacts with nanoparticles, reshapes their structure and changes their properties; thus modifies particles distribution, biotransformations and potential toxicity. As the understanding of nanoparticles processing, persistence, degradation and recycling will help predicting potential exposure risks, it is necessary to associate the concept of nanoparticles lifecycle to biological effects and employ (specific) methodologies to detect, quantify and follow the bioprocessing of nanoparticles in vivo over time, from the whole body level to the nanoscopic scale. Besides the composition, nanoparticles persistence/degradability is governed by their architecture and the nature/quality of the surface coating; therefore strategies can be adopted to control the long-term fate of nanoparticles in the organism. In this Opinion we focus on the lifecycle of magnetic iron oxide nanoparticles, a versatile and biocompatible class of nanoparticles, which found their way to clinical trials. (C) 2015 Elsevier Ltd. All rights reserved.