Extrapolating results of animal models to humans in real-life settings can be difficult; epidemiologic studies of the factors influencing the frequency and distribution of diseases in human populations are therefore critical to identifying human reproductive toxicants. Case reports, surveillance systems, and observational studies (including cross-sectional, case-control, and cohort designs) can be used, respectively, to generate hypotheses, estimate prevalence of disease in populations, and examine correlations between toxicant exposures and adverse reproductive outcomes. Major challenges in observational reproductive epidemiologic studies include exposure assessment, identifying all outcomes accurately (including when outcomes might be competing or not come to clinical attention) and addressing sources of bias. Examples of occupational and environmental exposures examined in observational epidemiologic studies include heavy metals, pesticides, organic solvents, dioxins and dioxin-like compounds, endocrine disruptors, exposures in the healthcare setting, tobacco use and second-hand smoke, and air pollution. Emerging areas of study include life-course epidemiology, epigenetics, and nanomaterials. As technology changes and new materials are used in industry, research on health effects of those materials will be needed. Improvements in our understanding of mechanisms of reproductive toxicity, improved sources of epidemiologic data, and new tools to evaluate past exposure promise to transform the study of reproductive epidemiology.