Thrombosis is the most frequent cause of mortality worldwide and is closely linked to haemostasis, which is the biological mechanism that stops bleeding after the injury of blood vessels. Indeed, both processes share the core pathways of blood coagulation and platelet activation. Here, we summarize recent work suggesting that thrombosis under certain circumstances has a major physiological role in immune defence, and we introduce the term immunothrombosis to describe this process. Immunothrombosis designates an innate immune response induced by the formation of thrombi inside blood vessels, in particular in microvessels. Immunothrombosis is supported by immune cells and by specific thrombosis-related molecules and generates an intravascular scaffold that facilitates the recognition, containment and destruction of pathogens, thereby protecting host integrity without inducing major collateral damage to the host. However, if uncontrolled, immunothrombosis is a major biological process fostering the pathologies associated with thrombosis.