Despite high overall immunization coverage levels among U.S. preschool children, areas of underimmunization, called pockets of need, remain. These areas, which pose both a personal health and a public health risk, are typically poor, crowded, urban areas in which barriers to immunization are difficult to overcome and health care resources are limited. The purpose of this report is to review barriers to immunization of preschool children living in pockets of need and to discuss current issues in the identification of and implementation of interventions within these areas. The Centers for Disease Control and Prevention administers a federal grants program that funds state and metropolitan immunization programs. This program promotes a three-pronged approach for addressing pockets of need: (1) identification of target areas, (2) selection and implementation of programmatic strategies to improve immunization coverage, and (3) evaluation of progress or impact. At each step, scientific evidence can guide programmatic efforts. While there is evidence that state and metropolitan immunization programs are currently making efforts to address pockets of need, much work remains to be done to improve immunization coverage levels in pockets of need. Public health agencies must take on a broadened role of accountability, new partnerships must be forged, and it may be necessary to strengthen the oversight authority of public health. These tasks will require a concentration and redirection of resources to support the development of an immunization delivery infrastructure capable of ensuring the timely delivery of immunizations to the most vulnerable of America's children.