A University College London-led research team elucidated the mechanism behind polymyxin B’s bactericidal action, revealing it disrupts bacterial outer membranes in an energy-dependent manner. Dormant or stationary phase bacteria evade killing due to inactive armor production, explaining persistence in chronic infections and inefficacy against dormant cells. Cellular activity facilitates membrane protrusions and shedding prompted by the drug, essential steps for bacterial eradication. This insight could inform development of combination therapies that sensitize dormant pathogens to antibiotics.