Vasopressin (AVP) and its receptors play a pivotal role in maintaining body homeostasis under physiological and pathophysiological conditions. As a consequence, the vasopressin system has emerged as an important target for both diagnostic and therapeutic applications in a number of medical conditions. Stoichiometric generation of AVP with copeptin, which is relatively accessible in the blood for measurements, makes copeptin a valuable surrogate of AVP. In this review, we present the regulation of release of AVP and activation of V1a, V1b, and V2 vasopressin receptors under physiological and pathological conditions. We make a survey of the role of AVP in: the regulation of the cardiovascular system; body fluid osmolality; natraemia; endocrine regulation; food intake; metabolism; circadian rhythmicity, immunological processes; and in the formation of learning, memory, cognition, and emotional and social behaviours. We also discuss the significance of the inappropriate functioning of the vasopressin system for: the development of cardiovascular diseases; disturbances of the water-electrolyte balance; energy metabolism; inflammatory processes; pain; neurogenic stress; memory disorders; depression; anxiety; autism; and schizophrenia. The structure and biological properties of peptide and non-peptide agonists and antagonists of V1a, V1b and V2 vasopressin receptors are presented and the potential use of copeptin and the current and likely indications for AVP agonists and antagonists in the diagnosis and therapeutics of multiple pathological conditions is discussed.