Asthma is recognized as a complex disease resulting from interactions between multiple genetic and environmental factors. Accumulating evidence suggests that respiratory viral infections in early life constitute a major environmental risk factor for the development of childhood asthma. Respiratory viral infections have also been recognized as the most common cause of asthma exacerbation. The advent of molecular diagnostics to detect respiratory viruses has provided new insights into the role of human rhinovirus (HRV) infections in the pathogenesis of asthma. However, it is still unclear whether HRV infections cause asthma or if wheezing with HRV infection is simply a predictor of childhood asthma. Recent clinical and experimental studies have identified plausible pathways by which HRV infection could cause asthma, particularly in a susceptible host, and exacerbate disease. Airway epithelial cells, the primary site of infection and replication of HRV, play a key role in these processes. Details regarding the role of genetic factors, including ORMDL3 , are beginning to emerge. This review discusses recent clinical and experimental evidence for the role of HRV infection in the development and exacerbation of childhood asthma and the potential underlying mechanisms that have been proposed.