An abundance of research has documented health inequalities by race and socioeconomic position (SEP) in the United States. However, conceptual and methodological challenges complicate the interpretation of study findings, thereby limiting progress in understanding health inequalities and in achieving health equity. Fundamental to these challenges is a lack of clarity about what race is and the implications of that ambiguity for scientific inquiry. Additionally, there is wide variability in how SEP is conceptualized and measured, resulting in a lack of comparability across studies and significant misclassification of risk. The objectives of this review are to synthesize the literature regarding common approaches to examining race and SEP health inequalities and to discuss the conceptual and methodological challenges associated with how race and SEP have been employed in public health research. Addressing health inequalities has become increasingly important as the United States trends toward becoming a majority-minority nation. Recommendations for future research are presented. Expected final online publication date for the Annual Review of Public Health Volume 39 is April 1, 2018. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.