The membrane attack complex (MAC) is a critical effector of innate immune defence, responsible for killing pathogens but also implicated in causing damage to self-cells in disease. Upon activation, complement proteins assemble on target membranes to pierce holes in lipid bilayers. However, there were critical gaps in our understanding of how the membrane barrier is breached during MAC formation. We have now elucidated this process using an innovative combination of structural and biophysical techniques. The novelty of these structures provides new insights into how proteins cross lipid bilayers. This information is vital to our understanding of how the immune system fights infection and to our ability to improve therapeutics that regulate complement activity.