Health impact assessment (HIA) is a multidisciplinary method aimed at assessing the health effects of policies, plans, and projects using quantitative, qualitative, and participatory techniques. In many European countries, such as in Italy, there is a lack of implementation of HIA procedures and it would be necessary to develop instruments and protocols in order to improve the specific skills of professionals involved in the assessment process. This article aims to describe the development and implementation of HIA guidelines, promoted by the Italian National Agency for Regional Health Services (AGENAS), in 4 Southern Italian regions. Public health search engine and institutional Web sites were consulted to collect international data existing in this field. Monthly workshops were then organized with regional representatives to discuss the scientific literature and to identify the guidelines' contents: source of data, stakeholders, screening- and scoping-phase checklist tools, priority areas, monitoring, and reporting plans. Four regions (Calabria, Campania, Puglia, and Sicilia) took part in the project. This article describes the methodology of development and implementation of HIA guidelines in the Italian context. The tools created to collect data and assess health consequences (such as screening and scoping grids) are reported. This project represents the first structured initiative proposed and supported by the Ministry of Health aiming to introduce HIA in Italy. HIA should be considered a priority in the public health agenda, as a fundamental instrument in helping decision makers to make choices about alternatives to prevent disease/injury and to actively promote health.