Cell transplantation is a potential therapy for patients suffering from congestive heart failure. Many cell types have been experimentally tested for their ability to improve cardiac function. In this review, we discuss the potential of cell transplantation into the heart using various cell sources and introduce an attractive new cell source: Muscle-derived stem cells (MDSCs) are capable of delivering therapeutic genes and potentially differentiating toward a cardiomyocyte lineage within an injected heart. MDSCs are an attractive, alternate cell source because in addition to being multipotent (i.e., capable of differentiating into various lineages), they are easily accessible via simple biopsy of the patient's own muscle. This review will describe the isolation and unique characteristics of MDSCs and outline their potential use in regenerative medicine.