About 150 human rhinovirus serotypes are responsible for more than 50 % of recurrent upper respiratory infections. Despite having similar 3D structures, some bind members of the low-density lipoprotein receptor family, some ICAM-1, and some use CDHR3 for host cell infection. This is also reflected in the pathways exploited for cellular entry. We found that even rhinovirus serotypes binding the same receptor can travel along different endocytic pathways and release their RNA genome into the cytosol at different locations. How this may account for distinct immune responses elicited by various rhinoviruses and the observed symptoms of the common cold is briefly discussed.