CD4⁺ T helper (T_H) cells have crucial roles in orchestrating adaptive immune responses. T_H2 cells control immunity to extracellular parasites and all forms of allergic inflammatory responses. Although we understand the initiation of the T_H2-type response in tissue culture in great detail, much less is known about T_H2 cell induction in vivo. Here we discuss the involvement of allergen- and parasite product-mediated activation of epithelial cells, basophils and dendritic cells and the functions of the cytokines interleukin-4 (IL-4), IL-25, IL-33 and thymic stromal lymphopoietin in the initiation and amplification of T_H2-type immune responses in vivo.