Coronary artery disease (CAD) is exceedingly prevalent and requires care optimization. Regenerative medicine holds promise to improve the clinical outcome of CAD patients. Current approach consists in subsidizing the infarcted heart with boluses of autologous stem cells from the bone marrow. Moreover, mesenchymal stem cells (MSCs) are in the focus of intense research owing to an apparent superiority in plasticity and regenerative capacity compared with hematopoietic stem cells. In this review, we report recent findings indicating the presence, within the heterogeneous MSC population, of perivascular stem cells expressing typical pericyte markers. Moreover, we focus on recent research showing the presence of similar cells in the adventitia of large vessels. These discoveries were fundamental to shape a roadmap toward clinical application in patients with myocardial ischemia. Adventitial stem cells are ideal candidates for promotion of cardiac repair owing to their ease of accessibility and expandability and potent vasculogenic activity.