The study area is located along the Dead Sea Rift, the climate is considered arid in its southern margin near the Dead Sea, which is the lowest water reservoir found on the globe (412 m BSL), to semiarid in its northern part. During the last few decades, the water resources became depleted limiting the natural development of the agricultural settlements, which are the most common type of communities in the region. Previous studies suggested that a large amount of freshwater is lost as the result of salinization processes, which occur when fresh groundwater from the mountain aquifers, flow into the saline clastic Neogene aquifer complex. In order to comprehend this complex system, a detailed outlining of the regional hydrogeological system is essential. Since there are no boreholes, which penetrate the aquiferous rock sequences within the Rift, it was necessary to interpolate a large variety of data from several fields of geosciences. The methods applied included geological mapping, geophysical modeling based on interpretation of seismic profiles and geochemical modeling based on chemical and isotopic analysis of runoff, sediments and groundwater. The combined modeling based on results from the different types of analyses implied to several conclusions relevant to the regional water management policy: (1) groundwater becomes saline as it flows from the margins of the Rift to its center. Therefore, it is recommended to exploit it along the foothills of the rift escarpment. (2) Geophysical modeling indicated that the foothills and the Karstic mountain aquifer extend into the subsurface of the valley and can be farther exploited (up to 15 mm3 per annum) by relatively shallow wells. (3) Several mechanisms of groundwater salinization were deciphered: (a) the dense vertical faulting systems act as potential conduits for saline water, which flow-up from deep-seated sources and penetrate into the fresh aquifers. (b) Fresh groundwater in the clastic aquifer complex is rare, furthermore, two evaporates bodies were encountered (Auja and Zaharat el Qurein), also acting as sources for fresh water salinization. (c) Although the quantity of runoff recharge to the Jordan Valley aquifer complex is negligible, the increase in its salt-content (TDS) turns this negligible freshwater recharge to a significant contributor of salts.