The phytohormone ABA mediates many physiological and developmental responses, and its key role in plant water relations has fueled efforts to improve crop water productivity by manipulating ABA responses. ABA's core signaling components are encoded by large gene families, which has hampered functional studies using classical genetic approaches due to redundancy. Chemical approaches can complement genetic approaches and have the advantage of delivering both biological probes and potential agrochemical leads; these benefits have spawned the discovery and design of new chemical modulators of ABA signaling and biosynthesis, which have contributed to the identification of ABA receptors and helped to define PYR1 and related subfamily III receptors as key cellular targets for chemically manipulating water productivity. In this review, we provide an overview of small molecules that have helped dissect both ABA signaling and metabolic pathways. We further discuss how the insights gleaned using ABA probe molecules might be translated to improvements in crop water productivity and future opportunities for development of small molecules that affect ABA metabolism and signaling.