Human rhinovirus (HRV) affects the lower and upper respiratory tract, however, some studies suggest that HRV infection can lead to extrapulmonary complications in critical illness. Moreover, some reports have shown the presence of HRV in patients with Central Nervous System (CNS) disease. During a CNS infection, the microglia cells are the first line of defense against pathogens. In this study, the susceptibility of the human microglial clone 3 cell line (HMC3) to HRV infection was analyzed. Our findings demonstrate for the first time that HRV is capable of completing the entire viral cycle in microglial cells.