Efficient cardiac regeneration post-infarction (MI) requires the replacement of lost cardiomyocytes, formation of new coronary vessels and appropriate modulation of the inflammatory response. However, the human heart has an inadequate capacity to regenerate and insight into how to stimulate repair of the heart is currently limited. Our approach utilises the paradigm of understanding cardiovascular development to inform on adult myocardial and vascular regeneration. We previously demonstrated that the actin-binding peptide Thymosin β4 (Tβ4), required for epicardium-derived coronary vasculogenesis, can recapitulate its embryonic role and activate quiescent adult murine epicardial cells (EPDCs). Following coronary artery ligation (in isoflurane-anaesthetised mice) and stimulation with Tβ4, EPDCs facilitate neovascularisation of the ischaemic adult heart, leading to improved functional recovery. Our ongoing studies seek to determine whether EPDCs, under the guidance of Tβ4, can recapitulate a further role of the embryonic epicardium in stimulating myocardial growth. Support for such a role comes from studies by others in adult zebrafish in which the epicardium is reactivated post-injury to stimulate cardiomyocyte proliferation to achieve complete myocardial regeneration. Adult EPDCs are thus emerging as resident progenitors with the potential to sustain and repair the myocardium after ischaemic damage. The ability to revive the potential of these ordinarily dormant cells lies in the identification of key stimulatory factors, such as Tβ4, either via chemical screening or by elucidating the molecular cues used in the embryo to orchestrate cardiovascular development.