The natural production of the beta-lactam antibiotic carbapenem in bacteria involves a group of enzymes that form a synthetic pathway as well as proteins that protect the cell from self-intoxification by the products. We report the crystal structure of CarF, one of the two proteins that confers resistance to the antibiotic synthesis in the host organism. The CarF fold places it within a widely occurring structural family, indicating an ancient structural origin from which the resistance function has been derived.