Regeneration of lost or injured tissues is very common in biology. Unfortunately, humans lack adequate regeneration in the heart and many other organs that are commonly ravaged by modern diseases. A revolution in stem cell biology has led to an explosion of interest in therapies that can awaken the regeneration potential in patients. In just the past decade, we have learned that any cell type from any patient, including cells from a blood sample or skin biopsies, can potentially be reprogrammed into a stem cell, and that patient’s stem cell can generate billions of new cells of a variety of differentiated cell types, including cardiomyocytes, endothelial cells and neurons. Stem cell biology is already changing how we approach human genetics and drug discovery, and clinical efforts to harness stem cell biology for heart failure are well underway. Here we predict that regenerative biology will initially struggle to hurdle economic and technical barriers for realistic treatments of heart diseases. However, regenerative biologists are beginning to design new approaches that were previously unimaginable, and ultimately regenerative medicine will have a profound impact for heart diseases.