Homeostasis of body fluid is a key component for maintaining health. An imbalance of body sodium and water causes various pathological states, such as dehydration, volume overload, hypertension, cardiovascular and renal diseases, and metabolic disorders. Conventional concepts regarding physiology and pathophysiology of body sodium and water balance have been established by several assumptions. These assumptions are that the kidneys are the master regulator of body sodium and water content, and that sodium moves inside the body in parallel with water. However, recent clinical and basic studies have proposed alternative concepts. These concepts are that body sodium and water balance are regulated by various organs and multiple factors, such as physical activity and the environment, and that sodium accumulates locally in tissues independently of the blood status and/or water. Various concerns remain unclear, and the regulatory mechanism of body sodium, fluid, and blood pressure needs to be readdressed. In the present review article, we discuss novel concepts regarding the regulation of body sodium, water, and blood pressure with a particular focus on the systemic water conservation system and fluid loss-triggered elevation in blood pressure.