The Neolithic revolution-the transition of our species from hunter and gatherer to cultivator-began approximately 14,000 years ago and is essentially complete for macroscopic food. Humans remain largely pre-Neolithic in our relationship with microbes but starting with the gut we continue our hundred-year project of approaching the ability to assess and cultivate benign microbiomes in our bodies. Buildings are analogous to the body and it is time to ask what it means to cultivate benign microbiomes in our built environment. A critical distinction is that we have not found, or invented, niches in buildings where healthful microbial metabolism occurs and/or could be cultivated. Key events affecting the health and healthfulness of buildings such as a hurricane leading to a flood or a burst pipe occur only rarely and unpredictably. The cause may be transient but the effects can be long lasting and, e.g., for moisture damage, cumulative. Non-invasive “building tomography” could find moisture and “sentinel microbes” could record the integral of transient growth. “Seed” microbes are metabolically inert cells able to grow when conditions allow. All microbes and their residue present actinic molecules including immunological epitopes (molecular shapes). The fascinating hygiene and microbial biodiversity hypotheses propose that a healthy immune system requires exposure to a set of microbial epitopes that is rich in diversity. A particular conjecture is that measures of the richness of diversity derived from microbiome next-generation sequencing (NGS) can be mechanistically coupled to-rather than merely correlated with some measures of-human health. These hypotheses and conjectures inspire workers and funders but an alternative is also consequent to the first Neolithic revolution: That the genetic uniformity of contemporary foods may also decrease human exposure to molecular biodiversity in a heath-relevant manner. Understanding the consequences-including the unintended consequences of the first Neolithic revolution-will inform and help us benignly implement the second-the microbial-Neolithic revolution.