Conventionally, megakaryocytes (MKs) are regarded as platelet-producing cells and their platelet-related functions in haemostasis have been well documented. However, it is increasingly evident that MKs have functions beyond platelet production. Convincing findings suggest that MKs are active participants in immunity and infections. Many reviews in the published literature have examined the immune functions of MK-derived platelets. However, relatively few reviews have emphasised on the role of MKs as immune cells. This review gives an overview of MKs, megakaryopoiesis and thrombocytopoiesis, as well as a thorough examination of the evidence that favours MKs as immune cells. The emerging and multifaceted contributions of MKs to host defence against various infections are also discussed. Together, these findings identify MKs as key players in both immune homeostasis and host-pathogen interactions, presenting new therapeutic opportunities.