Bacterial pathogens trigger cell death pathways in lung immune cells that cause inflammation, tissue damage and sepsis. We have now identified that triggering apoptosis of infected cells eliminates infections and dampens inflammation. We show that amongst the pro-survival BCL-2 family members, BCL-XL prevents apoptosis of infected cells. This is because, pathogens, such as Legionella inhibit host protein synthesis to disarm immune cells, which causes the loss of the related, but short-lived member, MCL-1. We demonstrate that BCL-XL is essential to establish infections by keeping the death factors, BAX and BAK, in check. Consequently, compounds that inhibit BCL-XL, originally developed to kill cancer cells, induce cell death of infected macrophages. Remarkably, a single dose of BCL-XL-targeted compound significantly reduces L. pneumophila burden in the lungs and prevents lethal bacterial infection in mice, in the absence of antibiotic therapy. Inducing apoptosis reduces the influx of inflammatory neutrophils and prevents excessive inflammation, commonly associated with infections. This demonstrates that anti-cancer drugs can be repurposed to kill infected cells and dampen inflammation.