With soil salinity levels rising at an alarming rate, accelerated by climate change and human interventions, there is a growing need for crop varieties that can grow on saline soils. Alfalfa (Medicago sativa) is a cool-season perennial leguminous crop, commonly grown as forage, biofuel feedstock, and soil conditioner. It demonstrates significant potential for agricultural circularity and sustainability, for example by fixing nitrogen, sequestering carbon, and improving soil structures. Although alfalfa is traditionally regarded as moderately salt-tolerant species, modern alfalfa varieties display specific salt-tolerance mechanisms, which could be used to pave alfalfa's role as a leading crop able to grow on saline soils. Alfalfa's salt tolerance underlies a large variety of cascading biochemical and physiological mechanisms. These are partly enabled by alfalfa's complex genome structure and out-crossing nature, which on the other hand entail impediments for molecular and genetic studies. This review first summarizes the general effects of salinity on plants and the broad-ranging mechanisms for dealing with salt-induced osmotic stress, ion toxicity, and secondary stress. Secondly, we address defensive and adaptive strategies that have been described for alfalfa, such as the plasticity of alfalfa's root system, hormonal crosstalk for maintaining ion homeostasis, spatiotemporal specialized metabolite profiles, and the protection of alfalfa-rhizobia associations. Finally, bottlenecks for research of the physiological and molecular salt-stress responses as well as biotechnology-driven improvements of salt tolerance are identified and discussed. Understanding morpho-anatomical, physiological, and molecular responses to salinity is essential for the improvement of alfalfa and other crops in saline land reclamation. This review identifies potential breeding targets for enhancing alfalfa performance stability and general crop robustness for rising salt levels as well as to promote alfalfa applications in saline land management.
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