This article addresses use of the Internet and Web 2.0 technologies by racial and ethnic minorities and explores the potential opportunities and challenges in leveraging Web 2.0 approaches to impact health disparities. These opportunities and challenges include developing approaches and methods to (a) identify strategies for integrating social media into health promotion interventions focused on major health-related issues that affect members of medically underserved groups; (b) amalgamate techniques to leverage and connect social-media technologies to other evidence-informed online resources; (c) integrate health communication best practices, including addressing health literacy issues; (d) capitalize on social networking to enhance access and communication with health care providers; and (e) advance current efforts and ongoing expansion of research participation by individuals from underserved communities.