Providing microbially safe water is a main goal of water supply to prevent endemic waterborne disease and outbreaks. Since increasing the level of safety requires resources, it is important to identify most relevant risks and efficient ways to reach health-based targets. Over the past decades, quantitative microbial risk assessment (QMRA) developed into a systematic, science-based approach to assess microbial risks through drinking water supply. In this study we present the QMRA approach and how it can be used to support decisions in both affluent and developing countries. This includes examples from the statutory QMRA in the Netherlands that led to efficient and effective improvements in water supply, not only in treatment, but also in monitoring and operation. In developing countries people often need to use various sources of drinking water. We will demonstrate how QMRA can help to improve insight in the relative risks of these routes and the effect of interventions.