The low temperature horizontal tube multi-effect desalination (MED) process is thermodynamically the most efficient of all thermal distillation processes. A comprehensive multi-disciplinary development and design approach resulted in prevention of corrosion and scale formation on the plant's heat transfer surfaces. It also allows the successful and most economical use of aluminum alloys for heat transfer tubes, as well as carbon steel epoxy coated shells for the evaporator body. The ability to use economically low grade heat, such as waste heat, exhaust steam from power station turbines as the primary heat source for MED, yields very low specific energy costs for sea water desalination. Recent developments of very economical low temperature deep pool nuclear heat reactors, when acting as the primary energy source for large MED plants, yield very low specific desalination energy costs The combination of economical specific MED plant costs with low energy cost, together with the inherent durability of low temperature MED avoiding the necessity of comprehensive sea water pretreatment (such as with RO plants) make the MED process one of the best candidates for safe and durable large capacity economical desalination options. This paper describes the design principles and various energy considerations that result in this uniquely economical MED process and plant. It also provides an overview of various cases of waste heat utilization, and cogeneration MED plants operating for many years.