Cell-based therapy is emerging as an innovative approach for the treatment of degenerative diseases, and stem cells appear to be an ideal source of cells for this. In cardiology, in particular, human embryonic stem cell (hESC)-derived cardiomyocytes theoretically fulfill most, if not all, of the properties of an ideal donor cell, but several critical obstacles need to be overcome. Many research projects are focusing on set-up strategies for directing hESC differentiation toward the cardiac lineage. It is one of the main difficulties in the search to provide a valuable source of cells to effect regeneration of myocardial tissue in patients with severe heart failure. To date, there are no easy and efficient protocols for the induction of hESC differentiation toward the cardiac lineage. Discovering new molecules or tools capable of doing this is imperative.