Drought and salinity stress are the major causes of historic and modern agricultural productivity losses throughout the world. Both drought and salinity result in osmotic stress that may lead to inhibition of growth. Salinity causes additional ion toxicity effects mainly through perturbations in protein and membrane structure. In contrast to animals, which rely on Na /K -ATPases for the expulsion of osmotica, plants rely on plasma membrane and endosomal ATPase activities to generate proton gradients to drive ion extrusion and intracellular sequestration. Consequently, most angiosperms, including all major crop species, have a diminished capacity for Na transport and tolerance to high salinity. New insights into the molecular mechanisms of Na /K discrimination, Na extrusion and compartmentation, water transport, and osmolyte biosynthesis and function have led to genetically engineered plants with improved salt, drought, and cold tolerance. A deeper understanding of the complex signal transduction and regulatory responses to osmotic stress promises novel strategies for improving salinity and drought tolerance that will be of practical benefit to agriculture.