The paper lists and reviews the issues, considerations and factors that faced planners in Israel in introducing large scale seawater desalination plants within the national and regional water supply systems. Most importantly, the paper quantifies the cost and benefit consequences of these factors, thereby establishing their relative weight, importance and significance. Cost consequences relate not only to the effect each factor had on desalinated water costs at their inlets to the national or regional water supply grids, but also to its effect on overall investments and operating costs related to expanding the entire water supply system to meet projected increases in demand, including seasonal, multi-seasonal and local storage capacities, distribution line sizes, pumping energy requirements, etc., and to dealing with deteriorating groundwater quality, including rehabilitation of salinized and/or contaminated wells, etc. Benefits included factors such as potable water supply reliability and quality enhancement, expanded and environmentally safer water reuse potential, etc. As will be shown, the challenge was to create a master plan which accounts for all these factors and optimizes their overall cost-benefit ratio both short and long term.