Inequalities with respect to the distribution of societal resources can predispose people to vulnerability, which has led to a growing concern across America. The Federal Government has taken a leadership role and has launched several initiatives to combat health inequalities experienced by vulnerable populations. The National Institute of Health and all of its institutes, including the National Institute of Nursing Research, have written strategic plans to reduce, and ultimately, eliminate such health disparities. Nursing research has been conducted in the setting of vulnerable populations; several theoretical models for studying vulnerability have been created; and interventional studies designed to reduce health disparities have been implemented. This introduction includes the following: (a) a definition of the concept of vulnerability and health disparities; (b) a discussion of the conceptual models of vulnerability and health disparity and their applications; (c) a description of the impact of federal funding on vulnerable populations research; (d) a synopsis of the contributions made by nurse researchers in the field of vulnerable populations research; and (e) an overview of the volume.