The Dead Sea is a hypersaline terminal lake located in a tectonic depression along the Dead Sea Transform. The regional paleogeographic setting began to take shape in the Miocene, and by the late Neogene fluvio-lacustrine sequences confined to the basin announced a new subsidence regime. Marine intrusion flooded the tectonic valley in the Pliocene, leading to the accumulation of a thick sequence of evaporites and initiated the development of the unique Ca-chloride brine of the basin. Rapid tectonic movements during the Pleistocene, or even earlier, disconnected the open sea and the valley became a deep, landlocked depression that hosted a series of lacustrine phases. The lakes deposited fine-laminated sequences during relatively wet phases and precipitated gypsum and halite during arid periods. The uppermost sedimentary fill comprises the Late Pleistocene Lisan Formation and the Holocene Ze’elim Formation. Lake Lisan existed during the last glacial period and in its highest stand extended from the Sea of Galilee to south of the Dead Sea, more than 200 m above the current level. The transition to the Holocene began with a dramatic dry-up recorded as a series of retreat strands on the margins of the basin and deposition of a thick halite unit. The Holocene Dead Sea was restricted to the deepest depression and its level fluctuated around 400 m below sea level in pace with climatic fluctuations dictated mostly by precipitation over the northern headwaters. The lake-water balance is a proxy for regional freshwater availability that influenced cultural transformations and demographic patterns during historical periods. The modern Dead Sea is being altered by intensified human activities. Water diversion and damming of freshwater for domestic and agricultural use, and brine evaporation for the potash industry have resulted in a level drop of over 1 m yr−1. The negative water balance has led to erosion of the exposed margins and development of sinkholes due to subsurface evaporite dissolution. The stable stratification of the lake-water column has diminished, and seasonal halite deposition characterizes the modern lake. The level drop has also resulted in drying and migration of spring seepages, putting unique ecosystems under threat. Currently, diversion of sea water from the Red Sea to the Dead Sea is viewed as a comprehensive solution for stabilizing the level as well as for producing hydroelectric power and desalinated water. However, this ambitious initiative must hurdle diplomatic tensions and financing difficulties, as well as intensive environmentalists’ objections.