Over the past 15 years, the invisible microbial world has taken center stage thanks to DNA sequencing methods that enable researchers to detect bacteria and other organisms that can’t be grown in culture. First these techniques revealed vast, diverse communities inside our guts, on our skin, inside buildings, and on every surface imaginable. Next, studies involving germ-free mice (that is, mice that lack microbes) and other research uncovered ties between these microbes, our so-called microbiota, and health – with bacteria playing potentially key roles in immunity, obesity, and development. So much has happened that in both 2011 and 2013 Science named the microbiome as one of its breakthroughs of the year and in 2012 and 2016 we published special issues on the topic. Today, Science strives to cover advances that reveal the specific ways in which the microbiota influences the physiology of the host, both in a healthy and in a diseased state and how the microbiota may be manipulated, either at the organismal or molecular level, to improve the health of the host. What’s hot right now is extending the role of microbes in human biology and recognizing that viruses, too, have an impact, and understanding how specific microbes and their products contribute to healthy and diseased states.