Knowledge about the human microbiome is requiring scientists to re-define the relationship between microbes and disease, going beyond Koch’s Postulates and incorporating concepts such as holobiont – understanding human physiology as the sum of the human body plus its microbiome– and pathobionts—microbes that cause disease only when certain conditions are met. Microbiome-based diagnostics are tools that allow detection of, and/or making prognoses on, human disease using microbial signatures of different types. Examples exist of potentially useful microbiome measurements at a disease site, or at a body site distant from the disease site. Causality between microbial signatures and disease is difficult to glean, yet in some cases microbiome signatures are useful diagnostically despite having no known causal relationship with the disease or condition in question. Mechanistic connections to disease are an active area of scientific inquiry. Companies globally are currently pursuing microbiome-based diagnostics or companion diagnostics for clinical use in a variety of diseases and conditions.