The traditional paradigm for obtaining a quantitative measurement in point-of-care (POC) assays may not be adequate for extremely resource-limited environments, such as remote villages in the developing world. In standard quantitative POC assays, sample volume and assay time must be controlled. Furthermore, thermally stable assay reagents, a power supply, and an electronic reader must be available. Arranging all of these variables in a single assay results in systems that are too complicated, expensive, and user-intensive for extremely resource-limited environments. This overview describes new approaches in various areas of materials science that are beginning to redefine how quantitative POC assays are achieved, with a focus on approaches that use paper as the platform for the assays. Such approaches should have an immediate impact in the developing world, but also may transform quantitative POC assays in a variety of other settings, where quantitative information about the health of people, plants, animals, and the environment would help individuals better assess and manage their lives.