The potency of specific transcription factors as cell fate determinants was first demonstrated by the discovery of MyoD, a master gene for skeletal muscle transdifferentiation. More recently, the induction of pluripotency in somatic cells using a combination of stem cell-specific transcription factors has been reported. That elegant study altered the approach to regenerative medicine and inspired new strategies for generating specific cell types by introducing combinations of lineage-specific transcription factors. A diverse range of cell types, such as pancreatic β-cells, neurons, chondrocytes, and hepatocytes, can be induced from heterologous cells using lineage-specific reprogramming factors. Furthermore, functional cardiomyocytes can be generated directly from differentiated somatic cells using several combinations of cardiac-enriched defined factors in the mouse. The present article reviews the pioneering and recent studies in cellular reprogramming and discusses the perspectives and challenges of direct cardiac reprogramming in regenerative therapy.