The capability of bone marrow derived cells to contribute to numerous peripheral tissues may hold tremendous promise for the field of regenerative medicine. In the context of skeletal muscle disease in particular, the ability of these cells to reach sites of damage through the circulation would overcome some key limitations of current cell therapy approaches. In muscle however, this non-classical repair process takes place at an exceedingly low frequency and fails to yield any measurable functional improvement. Recent advances regarding the cell types or mechanisms involved in this phenomenon may now provide direction for strategies aimed at increasing its efficiency to therapeutic levels.