Disparities are differences in health outcomes among groups that originate from sources including historically experienced social injustice and broadly defined environmental exposures. Large health disparities exist, defined by many factors including race/ethnicity, sex, age, geography, and socioeconomic status. Studying disparities relies on measures of disease burden. Traditional measures, such as mortality, may be less applicable to neurological disorders, which often lead to substantial morbidity and lower quality of life, without necessarily causing death. Measures such as disability-adjusted life-years or healthy life expectancy may be more appropriate for assessing neurological disease and permit comparisons across diseases and communities. There are many approaches that can be used to study disparities. Analyses of population-based observational studies, patient registries, and administrative data all contribute to the understanding of disparities in humans. Animal and other experimental designs, including clinical trials, may be used to identify mechanisms and strategies to reduce disparities. All of these approaches have strengths and weaknesses. Ultimately, understanding and mitigating disparities will require use of all of these methods. Crucially, a focus on not only improving outcomes among all individuals in society but minimizing or eliminating differences between those with better outcomes and those who have historically been disadvantaged should drive the ongoing investigations into disparities. This review is focused on epidemiological approaches to examining the depth and determinants of racial-ethnic disparities in the United States related to stroke, stroke care, and stroke outcomes.