A hallmark of chronic infections is an impaired immune response, enabling pathogens to persist. In a recent study, Khan, Downey et al. found that Mycobacterium tuberculosis infection in mice reprogrammes haematopoietic stem cells (HSCs) to limit myelopoiesis and impair trained immunity, a type of immunity that enhances the responsiveness of innate immune cells when they re-encounter pathogens. M. tuberculosis infection changed the transcriptional landscape of HSCs and impaired the generation of and intrinsic anti-mycobacterial capacity of bone-marrow-derived macrophages. M. tuberculosis infection caused changes in type I interferon signalling and dysregulated iron metabolism, which led to necroptosis in myeloid progenitors and a failure to generate trained immunity. Changes to transcriptional profiles of bone marrow HSCs and progenitors lasted for at least one year, suggesting that M. tuberculosis imprints a transcriptional profile that has lasting effects on innate immunity.