The Safe Schools/Healthy Students (SS/HS) Initiative offers a unique opportunity to conduct large-scale, multisite, multilevel program evaluation in the context of a federal environment that places many requirements and constraints on how the grants are conducted and managed. Federal programs stress performance-based outcomes, valid and reliable data, addressing important problems, ensuring efficiency and fiscal responsibility, reducing burden on federal staff and grantees, and developing and disseminating useful solutions and recommendations. MANILA Consulting Group, Inc., (MANILA), in partnership with Battelle Centers for Public Health Research and Evaluation (Battelle) and RMC Research Corporation (RMC), has been conducting the SS/HS national cross-site evaluation, which involves the coordinated efforts of federal Project Officers, local education agencies, technical assistance providers, communication specialists, and national and local evaluators across a diverse set of socioeconomic and cultural contexts. To date, the national cross-site evaluation has provided data indicating that the SS/HS Initiative is, in fact, meeting these goals. Findings revealed that fewer students reported they had experienced violence and fewer students reported they had witnessed violence. Fully 96 percent of school staff said SS/HS had improved school safety. There was a 263 percent increase in the number of students who received school-based mental health services and a 519 percent increase in those receiving community-based mental health services. In addition, more than 80 percent of school staff reported that they saw reductions in alcohol and other drug use among their students. These encouraging results stress the need for ongoing coordination at all levels of the Initiative to continue to ensure safer schools and healthier students. This article provides an overview of the initiative and introduces four articles in this special issue.