Vaccination represents one of the most powerful medical interventions on global health.Despite being safe, sustainable, and effective against infectious and in some cases also non-infectious diseases, it's nowadays facing general opinion's hesitancy because of a false perceived risk of adverse events. Adverse reactions to vaccines are relatively rare, instead, and those recognizing a hypersensitivity mechanism are even rarer. The purpose of this review is to offer a practical approach to adverse events after vaccination, focusing on immune-mediated reactions with particular regard to their recognition, diagnosis and management. According to clinical features, we propose an algorythm for allergologic work-up, which helps in confirming hypersensitivity to vaccine, nonetheless ensuring access to vaccination. Finally, a screening questionnaire is included, providing criteria for immunisation in specialized care settings.