Rhinoviruses and coronaviruses cause significant morbidity in immunocompetent people of all ages and in patients with underlying chronic medical or immunosuppressed conditions. Newer diagnostic tests, such as polymerase chain reaction (PCR), have expanded our understanding of these respiratory viruses in clinical infections. These sensitive diagnostic tests have been used to describe new members of these virus families, such as human rhinovirus C (HRVC) and human coronavirus NL-63 (HCoV-NL63). The epidemiology of these newly described viruses will help us develop better intervention strategies.