MDPI Antibiotics | For many years, both clinical and commercial factors have driven the development and use of broad-spectrum agents, with many positive results. However broad spectrum drugs can have an adverse effect on the intestinal microbiome. There is an increasing effort to develop narrow spectrum agents, as can be seen in the current pipeline and the growing number of narrow-spectrum and non-traditional agents being studied in response to the growth threat of widespread antibacterial resistance. This article co-authored by CARB-X Alliance Director Richard Alm, argues that despite the many challenges this type of research faces, this is encouraging and it is critical that it continues.