The nasal epithelium is the primary point of contact for inhaled respiratory viruses such as rhinovirus, respiratory syncytial virus, influenza, and coronavirus, among others. In order to establish infection, these viruses must engage their respective receptors located on host epithelial cells and begin replication. However, the nasal epithelium is also a pivotal orchestrator of both structural and innate immune defenses against these pathogens and thus mounts a broad antiviral response to halt the progression of the infection into the lower airways. Of note, the most common virus found in the airways of children presenting to the hospital emergency department with acute wheezing and asthma is rhinovirus C (RV-C), followed by rhinovirus A (RV-A). Here, we illustrate infection of a preclinical differentiated nasal epithelial model with clinical isolates of RV-A and -C, in conjunction with several methods utilized for characterization of epithelial responses post-infection in vitro.