Current treatment for chronic allergic airway disease with anti-inflammatory agents is effective but not specific, and is symptomatic rather than curative. The present review article outlines the involvement of T cells by dissecting the various steps in which naive CD4⁺ T cells differentiate to allergen-specific, activated T cells of the T_H2 type, which play a pivotal role in the pathogenesis of chronic allergic airway disease. Aiming at a concept for a highly specific therapy of this disease, various T cell costimulatory molecules (CD28, CD27, HVAM, BTLA, ICOS, OX40, CD30, 4-1BB, SLAM, CTLA-4, and PD-1) and the non-costimulatory molecule CD40L, all of them expressed on activated T_H2 effector T cells, are discussed as potential targets for an antibody-based therapy. Considering various criteria, including T-cell specific expression and expression characteristics on resting versus activated T cells, reasons are given why ICOS and OX40 can be regarded as optimal targets for such an immunotherapy. Furthermore, arguments are put forward that strongly favor an immunodepletion strategy as compared to an immunoblockade approach, when heading for a specific, long-lasting therapy of chronic allergic airway disease.