Vitamin A, and the retinoid system, play key roles in fundamental life processes. Metabolic and transcriptional machineries are in place in virtually all cells of all organs from the earliest stages of life and over the life-course. Proper performance of these machineries is required to fulfil the molecular and biochemical events that are needed for correct development and homeostasis. The retinoid system is susceptible to modulations by many and diverse categories of chemicals, and also to environmental chemical background exposures. National and international organizations and authorities have identified the retinoid system as a potential target for endocrine disruption and projects are ongoing to determine the scope of the problem and the need for regulatory action(s). In this context, this chapter provides state-of-the-art knowledge on the biology and toxicology of the retinoid system, and provides information on ongoing activities, which aim to better understand to what extent a modulated retinoid system may contribute to the increasing incidence of certain disorders in human and wildlife populations.