False-negative patch tests are clinically relevant. Skin hyporeactivity has been suggested as one possible cause. Evidence supports that failure to respond to a specific antigen might be due either to a faulty immune response, a defective inflammatory response or both. Thus, skin hyporeactivity may have clinical relevance in routine patch testing. Articles on this topic are infrequent and there is no index keyword for skin hyporeactivity as this phenomenon is poorly defined and investigated. This article summarizes several observations of skin hyporeactivity, reviews theories of possible mechanisms and discusses further consequences.