Abstract: Nanocrystals are promising in the delivery of poorly water-soluble drugs. However, information on the in vivo performance of nanocrystals is still not well understood. Physically embedded fluorophores in crystal lattice, i.e. the hybrid nanocrystals, enable bioimaging of nanocrystals. After a brief introduction to the up-to-date approaches to explore in vivo fates of nanocrystals, this article details the theoretical concepts as well as the techniques for the preparation and development of hybrid nanocrystals. Particular attention was paid to hybrid nanocrystals based on aggregation-caused quenching fluorescent probes as well as in vivo fates of nanocrystals via oral, intravenous and ocular routes obtained through this technique.