Recent evidence highlights novel roles for intracellular Na(+)/H(+) antiporters (NHXs) in plants. The availability of knockouts and overexpressors of specific NHX isoforms has provided compelling genetic evidence to support earlier physiological and biochemical data which suggested the involvement of NHX antiporters in ion and pH regulation. Most plants sequenced to date contain multiple NHX members and, based on their sequence identity and localization, can be grouped into three distinct functional classes: plasma membrane, vacuolar, and endosomal associated. Orthologues of each functional class are represented in all sequenced plant genomes, suggesting conserved and fundamental roles across taxa. In this review we seek to highlight recent findings which demonstrate that intracellular NHX antiporters (i.e. vacuolar and endosomal isoforms) play roles in growth and development, including cell expansion, cell volume regulation, ion homeostasis, osmotic adjustment, pH regulation, vesicular trafficking, protein processing, cellular stress responses, as well as flowering. A significant new discovery demonstrated that in addition to the better known vacuolar NHX isoforms, plants also contain endosomal NHX isoforms that regulate protein processing and trafficking of cellular cargo. We draw parallels from close orthologues in yeast and mammals and discuss distinctive NHX functions in plants.