The cardiac function critically depends on an adequate myocardial oxygenation and on a correct coronary blood flow. Endothelial, hormonal and extravascular factors work together generating a fine balance between oxygen supply and oxygen utilization through the coronary circulation. Among the regulatory factors that contribute to the coronary tone, increasing attention is paid to the cardiac endocrines, such as chromogranin A, a prohormone for many biologically active peptides, including vasostatin and catestatin. In this review, we will summarize the available evidences about the coronary effects of these molecules, and their putative mechanism of action. Laboratory and clinical data on chromogranin A and its derived fragments will be analyzed in relation to the scenario of the endocrine heart, and of its putative clinical perspectives.