Despite their role in healthcare provision, very little is known about how microbial (e.g. bacteria, Archaea and fungi) organisms are transmitted around the built infrastructure of a hospital (this knowledge limitation also applies to other built environments, but is especially critical in a hospital context). Here we will discuss our continued exploration of the hospital microbiome, including some of the key findings from these studies. The Hospital Microbiome Project is characterizing the taxonomic and functional composition of surface-, air-, water-, and human-associated microbial communities in a military and US private hospital to monitor changes in community structure following the introduction of patients and hospital staff, or major surgical procedures. The goal of the hospital study is to determine the influence of numerous factors on the rate and nature of microbial community succession in these hospitals including: human population demographics, how these demographics interface with a space, and the building materials, environmental conditions, and building operational characteristics used to create and maintain that space. This ongoing initiative is taking place in a newly constructed private US hospital in Chicago, where >15,000 samples are being collected using sterile swabs from patients, staff, rooms, common areas, water, and air filters from 52 or 365 time points prior to and following the official opening of the hospital. Absolute microbial abundance (plate counts and qPCR) and building environmental measurements (ventilation rates, temperature, relative humidity, light intensity, and human occupancy) are being combined with relative taxonomic and functional gene abundance via amplicon sequencing (16S/18S/ITS) and shotgun metagenomics. In our initial analysis we have found some interesting trends before and after occupation of the new hospital, and even between patient occupations of the same room, suggesting that the 70,000 bacterial taxa that call the hospital home are exploiting novel and interesting transmission routes.