The public health need for novel antimicrobial agents and therapeutic strategies is greater now than it has been since the advent of the antibiotic era in the 1940s. Infectious diseases remain the second leading cause of death worldwide, and more than 70% of the bacteria that cause hospital-acquired infections are resistant to at least one of the drugs most commonly used to treat them. In light of these facts, the conspicuous lack of novel agents in the drug discovery pipeline is particularly worrying and, even if the pharmaceutical industry were to step up efforts to develop new replacement drugs immediately, current trends suggest that some diseases will have no effective therapies within the next ten years.

The time has come for innovative, immediate action and, in response, the microbiology research community is fighting back. In recognition of ongoing efforts to develop new strategies to curtail the impact of infectious disease, Nature Reviews Microbiology has commissioned a special issue that focuses on exciting new developments in this area. This special issue is also accompanied by a Web Focus that draws together relevant articles from across the Nature Publishing Group — content that represents the cutting edge in the search for new ways to combat microbial infections.

There is no doubt that type-IV-secreted effectors have crucial roles in the virulence of some Gram-negative pathogens. Consequently, the type IV secretion pathway is an important target for exploitation in the development of novel antimicrobial strategies. In view of the complexity of the topic, this issue also includes a poster that summarizes our current knowledge of type-IV-secreted effectors and their effects on host cells.