Abstract: Steep concentration gradients of many ions are actively maintained, with lower concentrations typically located in the cytosol, and higher concentrations in organelles and outside the cell. The vacuole is an important storage organelle for many ions. The concentration gradient of cations is established across the plant tonoplast, in part, by high-capacity cation/H+ (CAX) exchange activity. While plants may not be green yeast, analysis of CAX regulation and substrate specificity has been greatly aided by utilizing yeast as an experimental tool. The basic CAX biology in Arabidopsis has immediate relevance toward understanding the functional interplay between diverse transport processes. The long-range applied goals are to identify novel transporters and express them in crop plants in order to “mine” nutrients out of the soil and into plants. In doing so, this could boost the levels of essential nutrients in plants.