The purpose of the Guide is to support national plant protection organizations (NPPOs) who wish to establish and maintain pest free areas (PFA) including places and/or production sites (PFPP and PFPS) as well as areas of low pest prevalence (ALPP). To facilitate an understanding of the processes to establish and maintain PFAs and ALPPs, a diagram in the form of a decision tree was constructed that identifies and outlines five general phases of programme development as follows: initiation, feasibility, establishment, maintenance, and market access phases. The guide is then divided into corresponding sections that describe what the key elements of each phase are, why these elements are important, what some of the common challenges and pitfalls are, and factors that may influence the success of the different phases such as budget stability, public outreach, availability of good survey and control tools, and open engagement with stakeholders and trading partners. By providing a deeper understanding of the factors that should be considered when establishing a PFA, PFPP, PFPS or ALPP the guide aims to overcome the challenges and maximize the impact of these efforts to the benefit of all parties. The guide concludes by providing a number of case studies from around the world that highlight successful PFA and ALPP programmes and how they deal with particular key issues. This guide contains current experience and the most advanced phytosanitary procedures in the implementation of PFA and ALPP, however, it is subjected to revision and updates as new developments are made available.