Host defence against microbial pathogens requires appropriate coordination of multiple signalling pathways. These pathways are triggered by innate immune recognition of conserved microbial molecules, and initiate an inflammatory cascade that involves recruitment of leukocytes to the site of infection, activation of antimicrobial effector mechanisms and induction of an adaptive immune response that promotes clearance of infection and long-term immune memory. Microbial pathogens possess specialized proteins termed virulence factors, which interfere with host defence at several levels. Many virulence factors from diverse pathogens have been identified in recent years and their functions linked to disruption of essential processes of immune defence, from signalling to phagocytosis. Although the diversity of pathogens and virulence factors is immense, common themes have emerged with regard to how microbial pathogens interfere with immune responses. Here we discuss recent advances in our understanding of how virulence factors target innate and adaptive immune responses, focusing on bacterial pathogens. We also propose that pathogens responsible for causing acute infection tend to target central components (hubs) of cellular signalling pathways, causing global disruption of the host response. By contrast, pathogens that cause chronic or persistent infections tend to target more peripheral signalling network components (nodes) to promote pathogen persistence.