For nearly a century, the adult heart was considered as a post-mitotic organ. The discovery of a resident cardiac stem cell (CSC) population in the heart has dramatically undermined this notion with the support of encouraging preclinical and clinical studies aiming to regenerate the damaged heart after a myocardial infarction (MI). There are two ways to obtain CSCs for transplantation: Allogeneic and autologous sources. Autologous cells may be obtained from the patients’ own tissue. Obtaining cells from diseased patients may contain a risk for altered stem cell characteristics. In addition to MI, these patients may also suffer from pathological conditions such as hypertension, diabetes mellitus, heart failure, congenital heart disease or cancer, which are known to alter CSC characteristics. It is also known that physiological conditions such as aging and death affect CSC functions in the heart. Our knowledge about the CSC characteristics in various physiological and pathological conditions may shed light on our opinion about the regenerative capacity and biological activity of these cells in these situations. Defining these properties may guide the researchers and clinicians in choosing and obtaining the most qualified CSC populations for cardiac regenerative medicine therapies. The purpose of this review is to describe the alterations in CSC characteristics in various physiological and pathological conditions.