In the past, human heart has been considered a post-mitotic organ formed by cells, like adult cardiomyocytes, terminally differentiated and incapable of proliferation. This paradigm has been shaken by recent works indicating that postnatal adult cardiomyocytes are able to re-enter in the cell cycle and proliferate. In this view, the understanding of main candidates regulating cardiomyocyte cell cycle is of vital importance for future clinical approach.