For many patients, lung transplantation is the only definitive treatment modality for different forms of end stage lung disease. However, the lung is rejected more often than any other type of solid organ allografts, and the five year survival is less than that of other transplanted organs. While alloimmunity directed against donor transplantation antigens is believed to be the key mechanism that mediates rejection responses, newer immunosuppressive regimens designed to abrogate alloimmune activation have not improved survival. Accordingly, these data suggest that other antigens are involved in rejection. Autoimmune responses, reported to occur during allograft rejection, could participate in graft destruction. This review article discusses the role of autoimmune responses to type V collagen ([col(V)], a minor collagen in the lung, in the pathogenesis of lung allograft rejection. By recognizing that lung transplant rejection involves both alloimmune and autoimmune responses, scientific investigation may uncover novel targets for therapeutic intervention that could prolong the life of the lung transplant recipient.