This special issue of Current Opinion in Pharmacology is concerned with new developments in antimicrobial drugs and covers innovative strategies for dealing with microbial infection in the age of multi-antibiotic resistance. Despite widespread fears that many infectious diseases may become untreatable, disruptive innovations are in the process of being discovered and developed that may go some way to leading the fight-back against the rising threat. Natural products, quorum sensing inhibitors, biofilm disruptors, gallium-based drugs, cyclodextrin inhibitors of pore-forming toxins, anti-fungals that deal with biofilms, and light based antimicrobial strategies are specifically addressed. New non-vertebrate animal models of infection may facilitate high-throughput screening (HTS) of novel anti-infectives.