Type I Signal Peptidase (SPase) is a bacterial protein that, until recently, was thought to be essential. Because of its key role it has been the target of much antibiotic development. A recent publication by scientists from The Scripps Institute has shown that bacteria have a “back-up plan” if SPase is inhibited. This back-up plan was previously unknown and can turn itself on when it senses that SPase is not adequately functioning. This work underscores the complications in developing effective antibiotics and the hazards of their overuse.