Na,K-ATPase (NKA) is well known for its role as a maintainer of electrolyte and fluid balance in cells, organs and whole body. Exciting new findings have revealed additional fundamental roles for NKA as a signal transducer and modulator of growth, apoptosis, cell adhesion and motility. The signal transduction function can be triggered by the binding of ouabain, the mammalian analogue of digitalis to NKA. The catalytic subunit of NKA exists in different forms and mutations in two of the forms that are expressed in brain can give rise to migraine, epilepsy and Parkinsonism-like symptoms. This review will present these new aspects of NKA and their clinical implications.