Several well-documented outbreaks of melamine poisoning have occurred in both animals and humans during the past 7 years, which led to the identification of melamine and cyanuric acid as nephrotoxins. This Review provides an overview of the known experimental and observational data (including toxicology, epidemiology, and pathology) concerning melamine contamination of foodstuffs, both alone and in combination with cyanuric acid. The various renal effects of ingestion of these compounds in both animals and humans are described, and a hypothesis on the mechanism of formation of melamine-based kidney stones is presented. Finally, the public health measures taken in the wake of the melamine contamination events are discussed.