For a long time, antibiotics have been ‘magical weapons’ to combat pathogenic microbes. The success of antibiotics is now greatly threatened by resistance to antibiotics and many scientists have already talked about the coming of the postantibiotic era. This special issue is prepared to understand recent research findings and new concepts about antibiotic resistance. Above all, this special issue explores mechanisms for the generation, selection, and spread of antibiotic resistance, and gives insight into what to target to prevent the development of antibiotic resistance. Just as antibiotics came from the concept of “magic bullet”, a breakthrough will come from a new concept based on a profound understanding of antibiotic resistance.