Clinical trials are currently underway to evaluate the benefit of dupilumab in treating allergic contact dermatitis (ACD). Dupilumab use has been reported to improve ACD reactions in some patients, but not all. Varying clinical responses to T helper 2 (TH2) inhibition challenge the classical view that ACD proceeds through a TH1-dominant pathway. Selective TH2 inhibitors, such as dupilumab, may attenuate ACD when the delayed hypersensitivity response is due to TH2-predominate activation; conversely, it may have no effect on ACD if it is elicited via TH1 or TH17 pathways. We hypothesize that allergen-specific T-cell responses and patient-specific factors both play an important role in determining which pathways are recalled in delayed hypersensitivity reactions.