Since heart cells normally lack the ability to regenerate, their malfunction or significant loss due to aging or diseases can lead to lethal consequences (e.g. heart failure and various forms of arrhythmias); myocardial repair is hampered by a severe shortage of donor cells and organs. Self-renewable, pluripotent human embryonic stem cells (hESCs) can provide an unlimited cell source for transplantation. Using a range of cell- and gene-based approaches for driven maturation and bioengineering, we have demonstrated in both small and large animal models that biological alternatives are superior to such conventional treatments as pharmacological and devicebased therapies. In this presentation, common hurdles in using hESCs for cardiac regeneration, their potential solutions and our latest progresses will be discussed.