Growth and regeneration of skeletal muscle fibers in response to injury are made possible by the presence of resident myogenic progenitor cells. Researchers have attempted to isolate and transplant these cells to regenerate new muscle in cases involving injury, disease, or genetic deficiencies. Reports from such experiments underscore the functional diversity of progenitors obtained from skeletal muscle; however, currently there is no reliable means by which to positively identify and isolate the most desirable muscle progenitor populations. Taking a cue from the hematopoietic community, researchers in this area have begun to investigate cell surface protein expression in progenitor populations. Previous findings in cultured myogenic cells and our results in cells obtained directly from dissociated muscle suspensions indicate that cells sorted based on their expression of the commonly-studied myogenic cell surface proteins Sca-1 and CD34 exhibit differing regenerative abilities. However, results obtained to date are insufficient to clearly delineate whether the expression of either of these proteins is an exclusive characteristic of efficient myogenic progenitors. Nonetheless, observations from these studies clearly suggest that progenitor heterogeneity should be an important consideration during the development and implementation of muscle regeneration strategies. Additional research is necessary to establish reliable selection criteria for the isolation of efficient progenitors, which will facilitate therapeutic discoveries and enhance our understanding of factors affecting regeneration outcomes.