The original Millennium Development Goal Target of reducing by half the portion of people without sustainable access to safe water supply and effective sanitation by 2015 was not achieved. Approximately 700 million people do not have access to an “improved” water supply, a billion more drink water from “unsafe” sources needing further improvement, and 2.5 billion lacked access to adequate sanitation. Lack of access to “safe” water is a global challenge requiring the development of revolutionary technologies and the creation of human resources capacity to scale-up and operate the technologies sustainably. This challenge can be addressed with revolutionary advances in water quality technologies and related fundamental sciences, and the development of sustainable, systems capable of producing an affordable, robust and reliable supply of safe drinking water to impoverished people worldwide. Such systems could integrate novel sensors that detect infective pathogens in real time coupled with robust treatment processes that destruct and/or remove these contaminants without producing toxic by-products. These developments should be paralleled by building partnerships that aim at creating capacity of human resources, developing microeconomic infrastructure, and facilitating acceptance by society.