Human rhinoviruses are the most common cause of viral respiratory infections across all age groups, from the neonate to the elderly patient. The benign nature of most of these infections as well as the difficulty to isolate the causative agent limits our perception of its real clinical impact. Molecular diagnostic tools have allowed to better characterize the variety of clinical presentations which are not limited to the common cold alone. It is now clearly established that rhinoviruses infect both the upper and lower tracheobronchial tree which may also be the site of viral replication. Moreover, the virus is the cause of significant complications in patients at risk such as those with asthma or highly immunocompromised hosts. The use of molecular screening techniques shows the very high diversity of circulating strains which are not only limited to known serotypes and has allowed the identification of new subgroups previously unknown. Detailed analysis of the genomic organization shows a common phylogeny between certain subgroups of rhinoviruses and enteroviruses and sheds light on the constraints modelling the evolution of human Picornaviridae. Furthermore, detailed analysis of the CRE structures shows that this structure is not only conserved for each species, but is also located on a specific region for each of these species.