The twentieth century was without doubt 'the age of the antibiotic'; all the known major antibiotic drug classes were identified, and the widespread use of antibiotics saw a substantial decrease in mortality and morbidity from common bacterial infections. However, that age is now well and truly over; the emergence of resistance to most commonly used antibiotics and the dwindling number of new antibiotics making it through the drug discovery pipeline pose a double threat to our continued protection from bacterial pathogens. In addition to limiting the spread of resistance through more prudent use of our current arsenal, it will become increasingly important to identify new classes of antibiotics and to develop alternative antimicrobial strategies that can replace antibiotics as they become ineffective. In this series of articles, Nature Reviews Microbiology highlights a number of alternative antimicrobial approaches that are currently being developed.