Exposure to endocrine disruptors varies geographically and temporally. Environmental levels of persistent organic pollutants have decreased after international regulation, whereas potential exposure to thousands of new chemicals has increased. The adverse effects of endocrine disruptors depend on susceptibility and timing of the exposure. Fetal and childhood exposures are often most harmful because of organizational and programming effects. In this review, we use the exposure to persistent organic pollutants such as polybrominated diphenyl ethers, dioxins and dioxin-like polychlorinated biphenyls and differences in the incidence of reproductive disorders between Denmark and Finland as an example to highlight how exposure variation and variation in genetic susceptibility may influence the strength of the association between the exposure to endocrine disruptors and adverse effects. Understanding the causes and implications of interindividual differences in susceptibility to endocrine disruptors is crucial for the protection of normal development.