Chemistry is the appropriate domain to start the discussion of what a zero concentration of a chemical means to human health, both from the perspective of the inability to detect that a compound is present and to realizing that there are minimum concentrations needed to interact with biological processes mediated by atoms and molecules. Chemistry is broadly defined as the branch of science that studies the structure, composition, and properties of elements, molecules and their derivatives as well as how they transform and interact with one another. After a brief history and overview of some basic principles of chemistry and measurement science, this chapter primarily deals with the strategies to detect chemicals, a field termed analytical chemistry. Chemists define zero as the absence of atomic or molecular structures, which in analytical chemistry, is operationally defined as not detectable by the instrument employed. Analytical techniques, methods of detection, and interpreting chemical assays will be introduced as well as defining and clarifying the meaning and differences in limits of detection versus limits of quantitation.