Many features of dystrophin-deficient muscle pathology are not clearly related to the loss of mechanical support of the muscle membrane by dystrophin. In the present review, evidence that supports a role for the immune system in promoting the pathology of dystrophinopathy is presented. The findings summarized here indicate that specific, cellular immune responses by cytotoxic T-lymphocytes and helper T-lymphocytes contribute to muscle pathology in dystrophin-deficient muscle, and that removal of specific lymphoid cell populations can reduce muscle pathology. In addition, innate immune responses may also promote dystrophinopathies by the tremendous infiltration of myeloid cell populations into the dystrophic muscle. Loss of normal redox homeostasis by dystrophin-deficient muscle may increase its sensitivity to free radical-mediated damage by myeloid cells. Collectively, the observations presented here suggest that the contribution of the immune system to dystrophinopathies may be significant, and that therapeutic approaches based upon immune interventions may ameliorate the pathological progression of dystrophin deficiency.