Powerful and/or selective extractant molecules/sorbents are a necessary component of efficient metal ion separation processes. However, selectivity in extraction and efficiency in process design often rely on reactions occurring in or moderated by the aqueous medium. This report describes the role of the aqueous phase and reactions that occur in aquo in defining separation efficiency and metal ion selectivity. As our programmatic focus is on actinide solution chemistry, the separations chemistry of the f-elements will be used to illustrate the principal role of aqueous chemistry in metal ion separations. Most of the arguments developed apply to metal ion separations chemistry and processes in general. The discussion will emphasize the role of complexation and the effect of properties of the aqueous medium on separation efficiency and selectivity. Historically important separations processes will be considered along with recent efforts in our laboratories to design and characterize new water soluble complexants for improved f element separations.