The transmission of scabies occurs with the burrowing of Sarcoptes scabiei var. hominis mites into the skin. Infestation invariably leads to the development of localized cutaneous inflammation, pruritus and skin lesions. Classical transmission studies document an initial increase in S. scabiei numbers subsequent to primary infestation with a gradual reduction as host immunity develops. However, certain individuals fail to control infection and develop severe crusting of the skin, accompanied with extremely high mite burdens, elevated antibody levels and eosinophilia. These individuals have the nonhealing form of the human disease known as crusted scabies. The genetic predisposition for susceptibility or resistance to S. scabiei infection in humans is hypothesized to correlate with the dominance of an IgE-driven Th2 response in severe disease or an interferon-gamma-dominated Th1 response that promotes parasite control. However, recent data reveals complexities in cytokine regulation in the skin and the mechanisms of acquired resistance and immune escape. In this review, we consider the recent immunological and biomolecular advances in understanding the human host immune response to S. scabiei infestations in the context of earlier studies and attempt to reconcile apparent differences and emphasize those aspects of the Th1/Th2 model that are supported or refined.