Next-generation sequencing (NGS) technologies together with an improved access to compute performance led to a cost-effective genome sequencing over the past several years. This allowed researchers to fully unleash the potential of genomic and metagenomic analyses to better elucidate two-way interactions between host cells and microbiome, both in steady-state and in pathological conditions. Experimental research involving metagenomics shows that skin resident microbes can influence the cutaneous pathophysiology. Here, we review metagenome approaches to study microbiota at this barrier site. We also describe the consequences of changes in the skin microbiota burden and composition, mostly revealed by these technologies, in the development of common inflammatory skin diseases.