Human rhinoviruses (RVs) are responsible for the majority of upper respiratory tract infections. Despite the high prevalence, the pathogenesis is incompletely understood. Experimental models would permit study of the immunological response to infections. Animal models have many limitations because of the anatomic and physiological differences between mammalian species. The only nonhuman animals susceptible to RV are chimpanzees and gibbons. Mouse models are not used because of host cell tropism of RV. This problem may have been partially overcome by transfecting mouse cells with viral RNA, by replacing mouse ICAM-1 with the human counterpart and by using a variant virus. It remains to be seen if these advances will translate into establishment of useful mouse models. In the absence of animal models, epithelial cell lines such as BEAS-2B, A549, 16HBE and HEp-2 have been used. Fibroblasts and smooth muscle cells have also been used. Although transformed cell lines have many properties in common with normal epithelial cells, they lose certain differentiated functions. Therefore, primary and recently well-differentiated cultures are used to study the immune response. In addition to a local inflammatory response, a systemic immune response to RV does develop; therefore peripheral blood mononuclear cells and dendritic cells have been infected with RV, shedding additional light on cell-mediated immunity. Cellular models are invaluable investigational tools for understanding mechanisms of RV-induced asthma and evaluating new targets for therapy.