Effective decontamination is a vital aspect of infection prevention and control, and has a crucial role in reducing healthcare-associated infections (HCAIs). Various decontamination methods can be used in healthcare settings to ensure that medical devices, equipment and the clinical environment are safe. It is essential for nurses and other healthcare staff to have adequate knowledge of the decontamination methods and infection prevention and control practices required to prevent HCAIs. This article discusses the most common HCAIs, decontamination methods that can be used, and relevant UK legislation, policies and guidance. It also outlines nurses’ responsibilities in relation to infection prevention and control and the importance of education and training in this area, with a particular focus on integrating human factors.