The purpose of the present narrative review, based on a PubMed search related to vasopressin, metabolism, and the cardiovascular system, is to summarize current information on the regulation of the secretion and action of arginine vasopressin (AVP) and insulin in context of their interactions in the regulation of blood pressure, tissue metabolism, and oxidative stress and to expose negative consequences of inappropriate cooperation of these two hormones in metabolic diseases, especially in obesity and diabetes mellitus. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.