Diseases caused by drug-resistant bacteria are a major threat to human health across the globe.From XDR-Tuberculosis to MRSA to the increasing threat from MDR-Gram-negative bacteria,the available arsenal of effective therapies continues to diminish.The discovery and development of novel antibacterials with activity against a spectrum of resistant pathogens has proven to be extremely challenging to the pharmaceutical and biotechnology industry.Future success will depend on the application of novel approaches to lead generation to identify novel chemical scaffolds that can target a spectrum of pathogens and overcome resistance.The application of new advances in areas such as high-throughput screening,fragment-based lead generation and improved modeling of in vivo efficacy,dose prediction and toxicology as well as a more complete understanding of mode of action and resistance development will be critical elements in the discovery of new antibacterials.