Swabbing the skin surface with a mild detergent to lift off the outer dead layers of skin and release the associated microbes has become the accepted best method to sample the microbiome (171). While some microbes have deeper reservoirs within the skin tissue, for example, within deeply embedded pilosebaceous units, swabs are much more tolerable to research subjects than biopsies for repeatedly sampling of the skin microbiota. After extracting DNA directly from the clinical sample, bacterial and fungal members of a skin community are identified by amplifying and sequencing 16S rRNA and ITS1 marker genes, respectively. 16S rRNA primers used to characterize the gut bacteria community failed to amplify Cutibacterium, a stumbling block rectifiable by amplifying the more 5′ region of the 16S rRNA (171, 172). Methods to make a sequencing library from the low biomass of a skin swab DNA opened up the possibility to perform skin shotgun metagenomic sequencing. After subtracting the human reads, shotgun metagenomic sequencing provides multikingdom (bacteria, fungi, virus) as well as strain-level analyses (6). The skin’s low microbial biomass created some challenges associated with air and reagent contaminants that could be monitored and controlled for with appropriate negative controls. Culturing isolates and performing whole-genome sequencing provides validation for strain level predictions and importantly provides resources for performing functional studies. Skin surface-associated bacteria persist by lowering their replication rate and perhaps even appearing as “quiescent” (173). Finding C. acnes in both cultures and shotgun metagenomic samples obtained by swabbing oily skin surfaces suggests that these microbes transit to the skin surface with terminally differentiating keratinocytes.