Intestinal commensals inhabit an anaerobic environment where conventional fluorescent protein tags are not functional. Now, Kasper and colleagues use bacterial biosynthesis and click chemistry to fluorescently label the polysaccharides that are shed from the capsules of commensal bacteria. As a first step, cultures are grown with an azide-modified sugar substrate of polysaccharide biosynthesis; next, click chemistry is used to covalently attach fluorescent dibenzocyclooctyne derivatives to the azide group. Application to Bacteroides fragilis showed that the label had no measurable effect on bacterial growth, carbohydrate metabolism or immunomodulation. The authors demonstrated that this method can be applied to in vivo imaging of host−anaerobe interactions, using intravital two-photon microscopy and non-invasive whole-body imaging to monitor B. fragilis in a mouse model of abscess formation and during colonization in germ-free mice.