Vaccine- and vaccination-related crises require a communication response that is different from the communication strategies used to promote the benefits and importance of vaccines in general. This document presents the technical guidance needed to develop a communication plan that is appropriate for managing crises related to vaccine safety. This guidance will be useful for managers in the areas of immunization and vaccine and vaccination safety. They will also help preparedness and response teams working in safety crises to optimize their communication plans in order to regain, maintain, or strengthen trust in vaccines, vaccination, and immunization programs in general. Each chapter presents a phase (preparation, implementation, and evaluation) with suggested actions and support tools to prepare, implement, and evaluate a communication response in a crisis situation. Also, some sections can also be used to strengthen routine national communication activities such as interaction with media, message generation, spokespeople preparation among others. The current document complements the Manual for the surveillance of events supposedly attributable to vaccination or immunization (ESAVI) in the Region of the Americas. This document is published within the framework of a joint project that aims to promote communication-related to safe vaccination in the Region of the Americas and support health authorities that need to develop a communication plan to manage crises related to vaccine safety. Some of the sections in this publication are based on the guidance documents available in the WHO Regional Office for Europe’s virtual library and can be consulted on their website.