Early-life wheezing-associated infections with human rhinovirus (HRV) are strongly associated with the inception of asthma. The immune system of immature mice and humans is skewed toward a type 2 cytokine response. Thus, HRV-infected 6-day-old mice but not adult mice develop augmented type 2 cytokine expression, eosinophilic inflammation, mucous metaplasia, and airway hyperresponsiveness. This asthma phenotype depends on interleukin (IL)-13-producing type 2 innate lymphoid cells, the expansion of which in turn depends on release of the innate cytokines IL-25, IL-33, and thymic stromal lymphopoietin from the airway epithelium. In humans, certain genetic variants may predispose to HRV-induced childhood asthma.