The concept of intersectional stigma combines theories on intersectionality with those on stigma related to multiple marginalized social positions and identities. This conception is critical to understanding its manifestation, its effect on HIV prevention and care, and its implications for addressing health disparities. HIV-related disparities originate in systems that differentially structure power and privilege for groups at distinct intersectional sociodemographic positions (e.g., race, ethnicity, sexual and gender identity). Although intersectional stigma is a useful analytic and conceptual lens for the study of HIV prevention and care research, designing and conducting studies to measure and address it bring conceptual and methodological challenges. Stigma reduction interventions that set out to address stigma but do not do so from an intersectional perspective and that do not account for multiple manifestations of stigma may not be effective in reducing stigma and, in turn, improving HIV-related outcomes.