An increasing number of researchers have investigated the influence of various environmental pollutants on the incidence of autism spectrum disorders (ASD). It is important to understand the environmental causes of autism not only from a medical perspective but also from the government policy viewpoint. Based on the review of recent literature, we would postulate that research on the environmental epidemiology of ASD is subject to at least five challenges: (1) Definitional challenges, stemming from multiple etiologies for ASD; (2) multiple biochemical pathways underlying ASD, such as oxidative stress and cytokine storm, obscuring the cause-effect relationship; (3) vast number of environmental pollutants; (4) confusion between the group level and individual level findings; and (5) cross-sectional as opposed to longitudinal nature of much of research. We believe that addressing these challenges can substantially improve the validity of environmental epidemiology of ASD research and assist in the clarity of understanding of some significant issues in public health.