The current paradigm suggests that monocyte fate and function are dictated by local signals at the site of infection. However, new data indicate that monocyte education begins in the bone marrow. Askenase et al. noted that as early as 4 days after an acute gastrointestinal infection, LY6Chi monocytes with the potential to mount regulatory responses were detected in the bone marrow and blood. Acquisition of this regulatory phenotype preceded monocyte recruitment to the gut, systemic inflammation and intestinal pathology, and it was shown to depend on interferon-g (IFNg). Early production of interleukin-12 by Batf3-dependent dendritic cells in the mucosal-associated lymphoid tissue was shown to activate natural killer cells in the bone marrow and induce their production of IFNg, which primes bone marrow-resident monocytes for regulatory function.