Economic evidence on the cost and benefits of sanitation and drinking-water supply supports higher allocation of resources and selection of efficient and affordable interventions. The study aim is to estimate global and regional costs and benefits of sanitation and drinking-water supply interventions to meet the Millennium Development Goal (MDG) target in 2015, as well as to attain universal coverage. Input data on costs and benefits from reviewed literature were combined in an economic model to estimate the costs and benefits, and benefit-cost ratios (BCRs). Benefits included health and access time savings. Global BCRs (Dollar return per Dollar invested) were 5.5 for sanitation, 2.0 for water supply and 4.3 for combined sanitation and water supply. Globally, the costs of universal access amount to US$ 35 billion per year for sanitation and US$ 17.5 billion for drinking-water, over the 5-year period 2010–2015 (billion defined as 109 here and throughout). The regions accounting for the major share of costs and benefits are South Asia, East Asia and sub-Saharan Africa. Improved sanitation and drinking-water supply deliver significant economic returns to society, especially sanitation. Economic evidence should further feed into advocacy efforts to raise funding from governments, households and the private sector.