Pioneering investigations conducted over a half century ago on tonicity, transcapillary fluid exchange, and the distribution of water and solute serve as a foundation for understanding the physiology of body fluid spaces. With passage of time, however, some of these concepts have lost their connectivity to more contemporary information. Here we examine the physical forces determining the compartmentalization of body fluid and its movement across capillary and cell membrane barriers, drawing particular attention to the interstitium operating as a dynamic interface for water and solute distribution rather than as a static reservoir. Newer work now supports an evolving model of body fluid dynamics that integrates exchangeable Na(+) stores and transcapillary dynamics with advances in interstitial matrix biology.