Protecting the health of the U.S. Latinx population is critical to the public health of the nation. Disproportionate health burden and inequitable opportunities for health and access to healthcare are barriers encountered by many U.S. Latinx populations. This chapter orients the reader to the terminology used to refer to members of Latin American descent in the United States and describes key demographics of the U.S. Latinx population. It reviews the literature on health status and the social and structural determinants of burden, healthcare access, and quality for U.S. Latinx populations; presents Latinx-specific models of health disparities/health equity; describes emerging interventions, programs, and policies for achieving health equity in this population; and offers best-practice recommendations in designing such efforts. The chapter then illustrates select best-practices with a case study. Interventions and programs targeting Latinx populations must consider the role of the current hostile environment toward immigrants and Latinx persons.