This article will review the utility of comparative animal models in understanding the molecular biology of ion transport. Due to the breadth of this field some 'disclaimers' need to be established up front. 'Comparative' will be defined as non-mammalian. 'Genetic species' will be defined as organisms that have been selected as models for genetic studies and for which the genome has been largely sequenced. 'Non-genetic species' will include other non-mammalian organisms. The review will be limited to ions that play a major role in extracellular (EC) ionoregulation (Na/K/Ca/Cl) and not to micronutrients (Fe) or heavy metals (Cd, Zn). The review will focus only on ion motive proteins that have been associated with vectorial transfer at epithelial tissues. The review is therefore intended as a guidepost to researchers new to the field as well as to inform biologists of the power of comparative genomics.