The observation of a much-improved fitness of wild-type plants over abscisic acid (ABA)-deficient mutants during drought has led researchers from all over to world to perform experiments aiming at a better understanding of how this hormone modulates the physiology of plants under water-limited conditions. More recently, several promising approaches manipulating ABA biosynthesis and signaling have been explored to improve water use efficiency and confer drought tolerance to major crop species. Here, we review recent progress made in the last decade on (i) ABA biosynthesis, (ii) the roles of ABA on plant-water relations and on primary and secondary metabolisms during drought, and (iii) the regulation of ABA levels and perception to improve water use efficiency and drought tolerance in crop species.