Although there has been a relentless increase in resistance to antimicrobial agents amongst important bacterial pathogens throughout the world, it is well known that the number of new antimicrobial agents being brought to the market has undergone a steady decline in the past several decades. There are a number of reasons for this, which are detailed in this article, but there is also a great deal of continuing research to find new effective antimicrobials, much of it now being carried out in academic centres and especially in small biotechnology companies, rather than by large pharma. Whilst classic screening methods and chemical modification of known antimicrobial agents continue to produce potential leads for new antimicrobial agents, a number of other approaches are being investigated. These include the search for potentiators of the activity of known antimicrobial agents and the development of hybrid agents, novel membrane-active drugs, and inhibitors of bacterial virulence and pathogenesis. A number of new bacterial targets are also being exploited, as are bacteriophages and their lytic enzymes. Given the amount of investigation presently underway, it is clear that although the antibiotic pipeline is not as promising as it was half a century ago, it is far from dry.