The microbiome, or the collections of microorganisms present in the body, is known to affect human health and disease and researchers are thinking about new ways to use them as next-generation diagnostics and therapeutics. Today bacteria from the normal microbiome are already being used in their modified or attenuated form in probiotics and cancer therapy. Scientists exploit the microorganisms’ natural ability to sense and respond to environmental- and disease-related stimuli and the ease of engineering new functions into them. This is particularly beneficial in chronic inflammatory diseases like inflammatory bowel disease (IBD) that remain difficult to monitor non-invasively. However, there are several challenges associated with developing living diagnostics and therapeutics including generating robust sensors that do not crash and are capable of long-term monitoring of biomolecules.