Since the 1980s, a number of bioactive molecules, now known as cardiovascular hormones, have been isolated from the heart and blood vessels, particularly from the subset of vascular endothelial cells. The natriuretic peptide family is the prototype of the cardiovascular hormones. Over the following decade, a variety of hormones and cytokines, now known as adipokines or adipocytokines, have also been isolated from adipose tissue. Leptin is the only adipokine demonstrated to cause an obese phenotype in both animals and humans upon deletion. Thus, the past two decades have seen the identification of two important classes of bioactive molecules secreted by newly recognized endocrine cells, both of which differentiate from mesenchymal stem cells. To assess the physiological and clinical implications of these novel hormones, we have investigated their functions using animal models. We have also developed and analyzed mice overexpressing transgenic forms of these proteins and knockout mice deficient in these and related genes. Here, we demonstrate the current state of the translational research of these novel hormones, the natriuretic peptide family and leptin, and discuss how lessons learned from excellent animal models and rare human diseases can provide a better understanding of common human diseases.